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ABSTRACT: Abstract Background and Objective: Postmortem studies indicate that the number and density of glial cells are reduced in different brain regions of patients with depression. Glial cell line-derived neurotrophic factor (GDNF) plays an important role in the pathogenesis of depressive disorder (DD) and might be a biomarker for damage to nerve cells. In this study, we compared the therapeutic effects of electroacupuncture (EA) and fluoxetine, a serotonin reuptake inhibitor, on DD patients, focusing on the serum level of GDNF. Design: This was a prospective, randomized clinical trial. Setting: Seventy-five patients with DD from the Department of Acupuncture, Beijing Hospital of Traditional Chinese Medicine, were recruited. Intervention: Twenty patients were treated with acupuncture for 6 weeks on the acupoints of Baihui (DU20) and Zusanli (ST36). Sixteen patients were treated with acupuncture for 6 weeks on the acupoints of Taichong (LR3), Sanyinjiao (SP6), Neiguan (PC6), and Shenmen (HT7), and constituted the electroacupuncture control group. The patients received acupuncture treatment five times per week. Twenty-five patients were treated with oral fluoxetine (20 mg/day) for 6 weeks. Outcome measures: All subjects were evaluated by the Hamilton Depression Rating Scale at four time points (0 [baseline], 2, 4, and 6 weeks after treatment). Serum GDNF was quantified in duplicate by enzyme-linked immunosorbent assay (ELISA). Results: EA and fluoxetine had similar curative effects on DD patients. EA had a faster onset of action, better response rate, and better improvement rate than fluoxetine. Both fluoxetine and EA treatment restored the normal concentration of GDNF in the serum of DD patients. Conclusion: EA treatment for depression is as effective as a recommended dose of fluoxetine. However, EA demonstrates an advantage in the regulation of the production of GDNF compared with fluoxetine.
Journal of alternative and complementary medicine (New York, N.Y.) 05/2013; · 1.69 Impact Factor
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ABSTRACT: A series of new bisbenzylisoquinoline alkaloids was partially synthesized from tetrandrine and fangchinoline and evaluated for their ability to reverse P-glycoprotein-mediated multidrug resistance (MDR) in cancer cells. All the test compounds increased the intracellular accumulation rate of rhodamine 123 in MDR cells (Bel7402 and HCT8), and most exhibited more potent MDR-reversing activity relative to the reference compound verapamil. Compounds 8, 10, 13, and 14 enhanced intracellular accumulation of doxorubicin in Bel7402 and HCT8 cells.
Journal of Asian natural products research 06/2012; 14(6):564-76. · 0.61 Impact Factor
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ABSTRACT: GL331, a topoisomerase II inhibitor, has been found to trigger DNA damage response (DDR) to induce cell cycle arrest. However, the underlying mechanism has not yet been fully understood. This study investigated the molecular mechanism involved in the GL331-induced cell cycle arrest via DDR in human hepatocellular carcinoma HepG2 cells. As a result, GL331 could induce S arrest and up-regulate the phosphorylation of the histone H2AX variant (γ-H2AX). Ataxia telangiectasia mutated protein kinase (ATM) was activated by GL331 through its autophosphorylation at Ser1981, which led to the activation of DNA damage signaling pathways including p53/p21 and Chk2/Cdc25A cascades. The DNA damage cascades triggered by GL331 finally induced the inactivation of cyclin A/Cdk2 complexes to some extent. These phenomena could be reversed by ATM siRNA, followed by a partial disruption of S arrest. The present results suggested that the S arrest induced by GL331 via DDR was in an ATM-dependent manner to some degree.
Journal of Asian natural products research 05/2012; 14(7):657-64. · 0.61 Impact Factor
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ABSTRACT: Bicyclol, an antihepatitis drug developed by Chinese scientists, has been shown to prevent the malignant transformation induced by 3-methylcholanthrene and 12-O-tetradecanoylphorbol-13-acetate in WB-F344 rat liver epithelial cells. This study provides further evidence on its role as a chemopreventive agent in experimental mice with diethylnitrosamine- (DEN-) initiated and phenobarbital- (PB-) promoted liver carcinoma. Liver tissue and serum were collected. In the two-stage model of hepatocarcinogenesis in mice, oral administration of bicyclol (100, 200 mg/kg) before DEN injection showed significant reduction in the incidence of hepatocellular foci, nodules, or carcinoma. Histopathological examination revealed that there was no hepatocellular carcinoma (HCC) and hepatoma formation in the mice pretreated with bicyclol (200 mg/kg) at week 20, while the mice treated with DEN/PB developed 33.3% HCC and 55.6% hepatoma. Furthermore, the serum levels of alanine aminotransferase (ALT), alkaline phosphatase (ALP), and α-fetal protein (AFP) in serum significantly increased in the DEN/PB model group in comparison with the control group. Pretreatment with bicyclol showed a marked reduction in the above condition. Bicyclol also decreased the expression of AFP and proliferating cell nuclear antigen level in the liver tissue and attenuated the decrease in body weight. In this study, we also found that 10 weeks after stopping the administration of PB and drugs, the control and bicyclol-treated (200 mg/kg) animals showed no HCC and hepatoma formation at the time of termination whereas DEN/PB-induced mice developed 100% hepatoma and 50% HCC. These results further indicate that bicyclol has the chemopreventive potential for liver carcinogenesis induced by carcinogens.
Journal of Biomedicine and Biotechnology 01/2012; 2012:584728. · 2.44 Impact Factor
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ABSTRACT: p53 (encoded by TP53) is undoubtedly one of the most extensively studied genes and proteins. It is a highly potent transcription factor which, under normal circumstances, is maintained at low level. Both genotoxic and non-genotoxic stresses can induce p53 stabilized leading to changes in the expression of p53-responsive genes. The biological outcome inducing this pathway can be either growth arrest and apoptosis or senescence to maintain the integrity of the genome or to delete the damaged cells. The biochemical activity of p53 itself and the cellular environment govern the choice between these outcomes in a cell type- and stress-specific manner. So, p53 is a pivotal tumour suppressor and a mainstay of our body's natural anticancer defence. This review could provide some useful information for further study on the mechanisms of tumorigenesis and its progression, and also could contribute to the discovery of antitumor agents.
Yao xue xue bao = Acta pharmaceutica Sinica 12/2011; 46(12):1413-9.
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ABSTRACT: To explore the influence of acupuncture treatment on proinflammatory cytokines of osteoarthritic (OA) cartilage.
Forty female SD rats were randomly and averagely divided into four groups: the normal, model, acupuncture and control group. The method of heel tendon resection for unilateral hind limb was used to establish OA animal models-that was to cut off the rat's heel tendon of left hind limb. The acupuncture group and control group were respectively treated by electro-acupuncture and Diclofenac on right hind limb of each animal for 2 weeks. Immunohistochemical staining was used to observe the expression characteristic of IL-1beta and TNF-alpha in cartilage of each group,and the differences were compared among the groups.
Both IL-1beta and TNF-alpha expression in model group were significantly up-regulated than those in the normal group (P<0.01). Their expression in model, acupuncture and control group were significantly different (P< 0.01). IL-1beta and TNF-alpha expression were significantly down-regulated in acupuncture and control group than that in model group (P<0.01), while the difference between the two former groups was not significant (P>0.05).
Acupuncture can down-regulate the expression of IL-1beta and TNF-alpha in osteoarthritic chondrocytes, and the regulating effect is the same as Diclofenac. This shows that acupuncture has a certain protective effect on osteoarthritic cartilage.
Zhongguo gu shang = China journal of orthopaedics and traumatology 09/2011; 24(9):775-8.
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ABSTRACT: Currently, multi-drug resistance (MDR) to anticancer drugs is a major obstacle to successful treatment of cancer. Looking for novel compounds with anti-MDR activity is an effectively way to overcome cancer drug resistance. Here, we found that H1, a novel derivate of Tetrandrine, displayed anti-MDR activity in vitro and in vivo. Average resistant factor of H1 is only 1.6. In KB and KBv200 cancer cells xenograft mice, H1 also displayed favorable anti-MDR activity. It could induce typical apoptosis as indicated by morphologic changes, DNA fragmentation in sensitive and resistant cancer cells. Further studies showed that H1 treatment resulted in the increase of ROS generation, elevation of the Bax/Bcl-2 ratio, loss of mitochondrial transmembrane potential (ΔΨ(m)), release of cytochrome c and AIF from mitochondria into cytosol, and activation of caspase-9 and caspase-3, but had no effect on activation of caspase-8 and the expression of Fas/FasL. On the other hand, H1 also inhibited survival pathways such as the activation of Erk1/2 and Akt1/2. In conclusion, H1 exerts good anti-MDR activity in vitro and in vivo, its mechanisms may be associated with initiating intrinsic apoptosis pathway and inhibiting the activation of Erk1/2 and Akt1/2. These findings further support the potential of H1 to be used in clinical trial of MDR cancer treatment.
Biochemical pharmacology 08/2011; 82(11):1593-603. · 4.25 Impact Factor
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ABSTRACT: H1 is a novel derivative of tetrandrine (Tet). Here we investigate the ability of H1 to reverse P-glycoprotein (Pgp)-mediated multidrug resistance (MDR) and its mechanisms.
KBv200, MCF-7/adr and their parental sensitive cell lines KB, MCF-7 were used for reversal study. The intracellular accumulation and efflux studies with Pgp substrates of doxorubicin and rhodamine 123 were determined by flow cytometry. The expression of Pgp was investigated by Western blot and RT-PCR analysis. ATPase activity of Pgp was performed by Pgp-Glo(™) assay systems. The ubiquitination level of Pgp was determined by immunoprecipitation analysis. The effect of ERK1/2 on Pgp expression in KBv200 cells were investigated by RNA interference.
H1 significantly potentiated the sensitivity of Pgp substrates in KBv200 and MCF-7/adr cells, but not in parental cells KB and MCF-7. H1 inhibited Pgp expression in KBv200 cells in a dose-dependent manner, but had no effect on MDR1 expression. Further studies showed that H1 prompted the degradation of Pgp and decreased Pgp protein half-life by enhancing the ubiquitination of Pgp, which may be related to downregulated MEK-ERK signal pathway. We also found H1 inhibited ATPase activity of Pgp in a dose-dependent manner.
H1 is an effectively and potential agent in reversing Pgp-mediated MDR by inhibiting the transport function and expression of Pgp.
Cancer Chemotherapy and Pharmacology 05/2011; 67(5):1017-25. · 2.83 Impact Factor
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ABSTRACT: To explore the curative mechanism of acupuncture treatment on osteoarthritis (OA).
Forty cases of female SD rats were randomly divided into a normal group, a model group, an acupuncture group and a medication group, 10 cases in each group. OA animal model was established by using the method of heel tendon resection for unilateral hind limb. The acupuncture group was treated with electroacupuncture at "Xiqian"(ST 35) and "Housanli"(ST 36), and the medication group with inunction of Diclofenac cream, and the normal group and the model group without any treatment. The expression of matrix metalloproteinase-1, 3 (MMP-1, MMP-3) and tissue inhibitor of metalloproteinase-1 (TIMP-1) in the cartilage were observed by immunohistochemistry.
There were significant differences among four groups. The expressions of MMP-1, MMP-3 and TIMP-1 in the model, acupuncture and medication groups were all significantly stronger than those in the normal group (all P < 0.01). The expressions of MMP-1 and MMP-3 in the acupuncture and medication groups were down regulated and TIMP-1 expression up-regulated with significant differences as compared with the model group (all P < 0.01), and the expressions of MMP-1 and MMP-3 in acupuncture group were significantly lower, while TIMP-1 expression significantly higher than that in the medication group (all P < 0.01).
Acupuncture can down-regulate the expression of MMP-1 and MMP-3 and up-regulate the expression of TIMP1, which is superior to that of Diclofenac cream, showing that acupuncture has a certain protective effect on cartilage from OA.
Zhongguo zhen jiu = Chinese acupuncture & moxibustion 03/2011; 31(3):241-6.
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ABSTRACT: ATP-binding cassette (ABC) transporters are a family of proteins that mediate multi-drug resistance (MDR) via ATP-dependent drug efflux pumps. Abnormally expression and function would result in tumor MDR. That is the most important mechanism of MDR. The inhibition of ABC transporters as a strategy to reverse MDR in cancer has been studied extensively. In this review, we reviewed the structure and function of ABC transporters, and focused on the research advances in the mechanism of tumors MDR mediated by ABC transporters and the development of their modulators and reversal strategies.
Yao xue xue bao = Acta pharmaceutica Sinica 10/2010; 45(10):1205-11.
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ABSTRACT: Eighteen schizandrin A derivatives, possessing an acyl group at 7-OH and/or halogen(s) at C-4 and C-11, were designed and synthesized for evaluation of their in vitro ability to inhibit multidrug resistance (MDR). They exhibit weak ability to restore the intracellular Rhodamine 123 in human hepatocarcinoma MDR cell lines Bel7402 and HCT8 relative to the reference drug verapamil.
Journal of Asian natural products research 07/2010; 12(7):549-56. · 0.61 Impact Factor
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ABSTRACT: To investigate the immunologic mechanism of acupuncture at Baihui (GV 20) and Zusanli (ST 36) for treatment of depression.
Eighty-four cases of depression patients were randomly divided into an electroacupuncture observation group (group A), an electroacupuncture control group (group B) and a medication control group (group C), 28 cases in each group. Baihui (GV 20) and Zusanli (ST 36) were used in the group A; Taichong (LR 3), Sanyinjiao (SP 6), Neiguan (PC 6) and Shenmen (HT 7) were used in the group B; and the group C was treated with oral administration of Fluoxetine. The scores of Hamilton Depression Scale (HAMD) were tested and the level of serum interleukin 1 (IL-1 beta), interleukin 6 (IL-6), and tumor necrosis factor alpha (TNF-alpha) were measured by Enzyme Linked Immunosorbent Assay (ELISA) before and after treatment.
Their scores of HAMD were obviously decreased after treatment in three groups (all P<0.01). In the group A, 2 cases were cured, 19 cases were markedly effective, 5 cases were effective and 2 cases were ineffective. In the group B, 16 cases were markedly effective, 12 cases were effective. While in the group C, 1 case was cured, 17 cases were markedly effective, 7 cases were effective and 3 cases were ineffective. The grade distribution of clinical effect showed that the effect of group A was better (P<0.05). The levels of serum IL-1 beta and IL-6 in the three groups were obviously decreased after treatment (P<0.05, P<0.01), while there was no significant difference between the level of serum TNF-alpha before and after treatment.
The effect of electroacupuncture observation group is superior to those of electroacupuncture control group and medication control group. All of these three methods can clear the inflammatory cytokines such as IL-1 beta and IL-6 away and improve the symptoms of depression.
Zhongguo zhen jiu = Chinese acupuncture & moxibustion 03/2010; 30(3):195-9.
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ABSTRACT: For the problems existed in the teaching of acupuncture manipulation and moxibustion method in western medicine college, for instance, the lack of credit hours and divorce from theory and practice, in addition to visualization teaching, this paper introduced case study and problem-centered teaching approaches. Besides clinical teaching, this paper emphasized anatomical knowledge which strengthen memory. In this way, the quality of teaching and teaching effects will be improved in the education of acupuncture manipulation and moxibustion method in western medicine college.
Zhongguo zhen jiu = Chinese acupuncture & moxibustion 01/2010; 30(1):75-6.
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ABSTRACT: 5-Bromotetrandrine (BrTet) was shown to overcome multi-drug resistance (MDR) in vitro and in vivo by inhibiting the overexpression and efflux function of P-glycoprotein in our previous study. The purpose of the present study was to evaluate the effect of BrTet on the sensitivity of doxorubicin (Dox) induced apoptosis in intrinsic resistant human hepatic cancer Bel7402 cells. The cells were treated with non-toxic concentrations of BrTet (1 microM, 2 microM, 4 microM) or the positive control drug verapamil (Vrp) (10 microM) for 24h followed by a low dose Dox (3 microM) for 24 h. The results showed that BrTet pretreatment followed by Dox led to typical apoptotic characters as indicated by morphologic changes, DNA fragmentation and changes in cell cycle, while the same dose of BrTet, Vrp and Dox alone did not induce apoptosis in Bel7402 cells. In addition, the pretreatment of BrTet or Vrp followed by Dox induced activation of caspase-3, release of cytochrome c and AIF from mitochondria into cytosol, loss of mitochondrial transmembrane potential (DeltaPsi(m)) and elevation of Bax/Bcl-2 ratio, with no effect on activation of caspase-8 and the expression of Fas/FasL. In conclusion, BrTet pretreatment enhanced the sensitivity of Dox to induce apoptosis by causing loss of DeltaPsi(m) and elevating the ratio of Bax/Bcl-2, eventually activated mitochondrial apoptotic pathway. These findings further support the potential of BrTet to be used in clinical trail of cancer treatment.
Cancer letters 12/2009; 292(1):24-31. · 4.86 Impact Factor
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ABSTRACT: To assess the anti-invasion effect of bicyclol (1) and its mechanism in human hepatocellular carcinoma (HCC) MHCC97-H cells with high metastatic potential. MTT assay was performed to evaluate the cytotoxicity of 1 to MHCC97-H cells and its inhibitory effect on the adhesion of these cells to laminin (LN) and fibronectin (FN). The anti-invasion effect of 1 was detected in an experiment using a transwell chamber. Transcription of vascular endothelial growth factor (VEGF), nm23-H1, and urokinase-type plasminogen activator receptor (uPAR) mRNAs was determined by an RT-PCR assay. The secretion and expression of alpha-fetoprotein (AFP) were analyzed by ELISA and flow cytometry, respectively. At concentrations of 10, 50, and 100 mumol/l, 1 obviously inhibited the adhesion of the MHCC97-H cells to LN and FN. The rates of inhibition of MHCC97-H cell invasion by 50 and 100 mumol/l for 1 were 37.3 and 50.2%, respectively. Drug 1 also decreased the expressions of VEGF, nm23-H1, and uPAR mRNA and the secretion of AFP in MHCC97-H cells. At low cytotoxic concentrations, the anti-hepatitis drug 1 demonstrated a significant anti-invasive effect in human HCC MHCC97-H cells with high metastatic potential. The inhibition of the expressions of VEGF, nm23-H1, and uPAR should contribute, at least in part, to the anti-invasion property of 1.
Journal of Asian natural products research 06/2009; 11(6):576-83. · 0.61 Impact Factor
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ABSTRACT: To compare therapeutic effects between body acupuncture and scalp acupuncture combined with body acupuncture on atherosclerotic cerebral infarction at acute stage.
Forty-two cases of atherosclerotic cerebral infarction at acute stage were divided into 2 groups. They were treated respectively by scalp acupuncture combined with body acupuncture and simple body acupuncture. The comprehensive scores of mind, speech, limb motor function, etc. of the patients before and after treatment were recorded and compared.
After treatment, the cumulative scores in the two groups reduced significantly (P < 0.01); the difference of scores before and after treatment in the scalp-body acupuncture group was significantly higher than that in the body acupuncture group (P < 0.05); there was no significant difference between the two groups in clinically effective rate (P > 0.05), but there was a very significantly difference between the two groups in the markedly effective rate (P < 0.01), the scalp-body acupuncture group being significantly higher than that in the body acupuncture group.
Acupuncture can improve mind, speech and limb motor function of the patient with atherosclerotic cerebral infarction at acute stage, and the therapeutic effect of scalp combined with body acupuncture is better than that of simple body acupuncture.
Zhongguo zhen jiu = Chinese acupuncture & moxibustion 01/2008; 28(1):10-2.
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ABSTRACT: ObjectiveTo assess the anti-invasive effect of DDB and its possible active mechanism in human hepatocellular carcinoma MHCC97-H with
high metastasis potential.
MethodsMTT assay was used to evaluate the cytotoxicity of DDB to MHCC97-H cells and the anti-adhesion of DDB on MHCC97-H cells to
laminin (LN) and fibronectin (FN). The anti-invasive effect of DDB was detected by the transwell chamber experiment. VEGF,
nm23-H1 and uPAR mRNA transcriptions were determined by RT-PCR assay. The secretion and expression of α-fetal protein (AFP)
were analyzed by ELISA and flow cytometry, respectively.
ResultsDDB at non-cytotoxic concentrations (10, 50 and 100 μmol/L) obviously inhibited the adhesion of MHCC97-H on LN and FN. In
the transwell chamber experiment, the inhibition rates of the invasion of DDB 50 and 100 μmol/L on MHCC97-H cells were 25.8%
and 32.3%, respectively. By RT-PCR assay, DDB 50 and 100 μmol/L decreased VEGF, nm23-H1 and uPAR mRNA expressions in MHCC97-H
cells. The ELISA assay showed that 50, 100 and 200 μmol/L DDB decreased the AFP secretion of MHCC97-H cells, the inhibitory
rates were 16.5%, 17.5% and 48.5%, respectively. DDB also decreased the expression of AFP in MHCC97-H cells by flow cytometry
assay.
ConclusionDDB, an anti-hepatitis drug, at non-cytotoxic concentrations showed significant anti-invasion effect in human hepatocellular
carcinoma MHCC97-H cells, and the inhibition of VEGF, nm23-H1 and uPAR expression should contribute to the anti-invasion property
of DDB.
The Chinese-German Journal of Clinical Oncology 12/2007; 7(1):2-6.
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ABSTRACT: DDB (dimethyl-4,4'-dimethoxy-5,6,5'6'-dimethylene dioxybiphenyl-2,2'-dicarboxylate) is a synthetic hepatoprotectant which has been widely used to treat chronic viral hepatitis B patients in China for more than 20 years. In this study, we evaluated DDB as a multidrug resistance (MDR) chemosensitizing agent.
A panel of sensitive and resistant cancer cell lines were treated with various concentration of DDB, and the effect on chemosensitivity and accumulation of anticancer drugs; promotion of apoptosis and P-glycoprotein (P-gp) expression were determined by MTT (Dimethyl thiazolyl-2,5-diphenyltetrazolium bromide) assay, fluorospectrometry and flow cytometry respectively. Drug resistance reversal activity of DDB was also examined in BALB/c nude mice bearing both acquired MDR human nasopharyngeal carcinoma KBv200 and parental KB xenografts. The effect of DDB on the pharmacokinetics of Dox and hematological toxicity induced by Dox was measured in ICR and C(57)/BL mice, respectively.
DDB at nontoxic concentrations of 12.5, 25 and 50 microM partly reversed the resistance to vincristine, doxorubicin, paclitaxel in acquired MDR breast carcinoma MCF-7/Adr cells, KBv200 and intrinsic MDR human hepatocarcinoma Bel(7402) cells, whereas no chemosensitizing effect of DDB was observed in sensitive KB and MCF-7 cells. DDB increased the intracellular accumulation of doxorubicin and inhibited surface P-gp expression in MCF-7/Adr cells. Furthermore, it was found that DDB promoted doxorubicin-induced apoptosis of Bel(7402) cells through enhanced caspase-3 activation. Co-administration of DDB at 300 and 500 mg/kg orally to nude mice increased the antitumor activity of vincristine to KBv200 xenografts without a significant increase in toxicity. In contrast, Co-administration of DDB did not inhibit the growth of KB xenografts. DDB also markedly reduced the decrease of leukocytes in doxorubicin-treated C(57)/BL mice. Co-administration of DDB increased Dox concentration in ICR mice bearing S180 sarcoma, but no pharmacokinetical interaction with Dox was observed.
These results indicate that DDB has MDR reversal activity by inhibiting P-gp and when used in combination with anti-cancer drugs, it could potentially be used as a clinical treatment for P-gp-mediated MDR cancers.
Investigational New Drugs 05/2007; 25(2):95-105. · 3.36 Impact Factor
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ABSTRACT: To optimize therapy of acupuncture and moxibustion for postsurgical gastroparesis syndrome (PGS).
Forty-one cases of PGS were randomly divided into 3 groups in order of visiting. Group A (n = 17) were treated by warming needle moxibustion, group B (n = 12) by acupuncture plus auricular point sticking, and group C (n = 12) by routine acupuncture. Changes of gastric drainage volume, therapeutic times and cured rate were investigated in the 3 groups.
All the 3 therapeutic methods could significantly decrease gastric drainage volume. The cured rate was 100.0% and the therapeutic times was (7.24 +/- 3.87) in the group A, 66.7%, (9.83 +/- 4.60) times in the group B and 75.0%, (15.25 +/- 3.81) times in the group C, with significant differences in the cured rate and the therapeutic times among the 3 groups (P < 0.05, P < 0.01).
The warming needle moxibustion is the best method for PGS, with less therapeutic times, high cured rate and rapid effect.
Zhongguo zhen jiu = Chinese acupuncture & moxibustion 03/2007; 27(3):173-5.
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ABSTRACT: Invasion and metastasis is the main cause of the poor prognosis and high mortality of hepatocellular carcinoma (HCC). Inhibiting invasion and metastasis is an effective approach to reduce the development and mortality of HCC. Dimethyl dicarboxylate biphenyl (DDB) is an old anti-hepatitis drug used in clinics. This study was to assess the inhibitory effect of DDB on adhesion and invasion of HCC cell line MHCC97-H with high metastasis potential, and explore its possible mechanism.
MTT assay was used to evaluate the cytotoxicity of DDB to MHCC97-H cells and the inhibitory effect of DDB on the adhesion of MHCC97-H cells to laminin (LN) and fibronectin (FN). The inhibitory effect of DDB on the invasion of MHCC97-H cells was detected by transwell chamber experiment. The mRNA levels of vascular endothelial growth factor (VEGF), nm23-H1, and urokinase-type plasminogen activator receptor (uPAR) were determined by reverse transcription-polymerase chain reaction (RT-PCR). The secretion and expression of alpha fetoprotein (AFP) were analyzed by ELISA and flow cytometry, respectively.
DDB at non-cytotoxic concentrations (10, 50 and 100 micromol/L) obviously inhibited the adhesion of MHCC97-H cells to LN and FN. The inhibition rates of the invasion of MHCC97-H cells were 25.8% and 32.3% after treatment of 50 and 100 micromol/L DDB, respectively; 50 and 100 micromol/L DDB also decreased the mRNA levels of VEGF, nm23-H1, and uPAR in MHCC97-H cells. The inhibition rates of AFP secretion of MHCC97-H cells were 16.5%, 17.5%, and 48.5% after treatment of 50, 100, and 200 micromol/L DDB, respectively; it also decreased the expression of AFP in MHCC97-H cells.
DDB, at non-cytotoxic concentrations, may obviously suppress the invasion of MHCC97-H cells through inhibiting VEGF, nm23-H1, and uPAR expression.
Ai zheng = Aizheng = Chinese journal of cancer 01/2007; 25(12):1464-9.
