Qian-Mei Zhou

Shanghai University, Shanghai, Shanghai Shi, China

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Publications (15)23.8 Total impact

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    ABSTRACT: Breast cancer remains the leading cause of cancer-related deaths among women. Owing to high efficiency and low toxic effects, further exploration of natural compounds from Chinese herbal medicine may be an efficient approach for breast cancer drug discovery. In this study, we investigated the effects of evodiamine on the growth and metastasis of MDA-MB-231 human breast cancer cells in vitro and in vivo. In vitro, evodiamine inhibited cell migration and invasion abilities through downregulation of MMP-9, urokinase-type plasminogen activator (uPA) and uPAR expression. Evodiamine-induced G0/G1 arrest and apoptosis were associated with a decrease in Bcl-2, cyclin D1 and cyclin-dependent kinase 6 (CDK6) expression and an increase in Bax and p27Kip1 expression. Moreover, evodiamine regulated p-ERK and p-p38 MAPK expression. Evodiamine-induced apoptosis was enhanced by its combination with the extracellular signal-regulated kinase (ERK) inhibitor PD98059 or the p38 mitogen-activated protein kinase (p38 MAPK) inhibitor SB203580. Evodiamine-inhibited metastasis was partly blocked by combination with PD98059 or SB203580. In vivo, the administration of evodiamine (10 mg/kg) significantly reduced tumor growth and pulmonary metastasis. These results demonstrate that evodiamine possesses antitumor activities via inhibition of cell migration and invasion, arrest of the cell cycle and induction of cell apoptosis in MDA-MB-231 cells.
    Oncology Reports 05/2013; · 2.30 Impact Factor
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    ABSTRACT: Metastasis is the major cause of death in breast cancer patients. In this study, we investigated the effects of baicalin, a natural compound, on migration, invasion and metastasis in the experimental breast cancer in vitro and in vivo and its mechanisms. It was found that baicalin not only dose-dependently inhibits MDA-MB-231 cells migration and invasion in vitro, but also suppresses the tumor growth and the pulmonary metastasis in MDA-MB-231 breast cancer xenograft model without body weight, liver and kidney functions changes in vivo. Further experiments showed that baicalin decreases Metalloproteinase (MMP)-2 and MMP-9 secretion, and the levels of MMP-2, MMP-9, urokinase-type plasminogen activator (uPA) and uPA receptor (uPAR) expressions in MDA-MB-231 cells. Moreover, it was also found that baicalin not only suppresses the p38 mitogen-activated protein kinase (MAPK) phosphorylation and expression, but also as well as p38MAPK inhibitor SB203580 or combined with SB203580 reduces MMP-2, MMP-9, uPA and uPAR expressions and MDA-MB-231 cells invasion. Therefore, we inferred that baicalin suppresses the migration, invasion and metastasis of MDA-MB-231 cells in vitro and in vivo possibly were by down-regulating MMP-2, MMP-9, uPA and uPAR expressions and involved in p38MAPK pathway.
    Anti-cancer agents in medicinal chemistry 01/2013;
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    ABSTRACT: Traditional Chinese medicine (TCM) treatment is regarded as a safe and effective method for many diseases. In this study, the characteristics among excessive, excessive-deficient, and deficient syndromes of Hepatocellular carcinoma (HCC) were studied using miRNA array data. We first calculated the differentially expressed miRNAs based on random module t-test and classified three TCM syndromes of HCC using SVM method. Then, the weighted miRNA-target networks were constructed for different TCM syndromes using predicted miRNA targets. Subsequently, the prioritized target genes of upexpression network of TCM syndromes were analyzed using DAVID online analysis. The results showed that there are distinctly different hierarchical cluster and network structure of TCM syndromes in HCC, but the excessive-deficient combination syndrome is extrinsically close to deficient syndrome. GO and pathway analysis revealed that the molecular mechanisms of excessive-deficient and deficient syndromes of HCC are more complex than excessive syndrome. Furthermore, although excessive-deficient and deficient syndromes have similar complex mechanisms, excessive-deficient syndrome is more involved than deficient syndrome in development of cancer process. This study suggested that miRNAs might be important mediators involved in the changing process from excessive to deficient syndromes and could be potential molecular markers for the diagnosis of TCM syndromes in HCC.
    Evidence-based Complementary and Alternative Medicine 01/2013; 2013:324636. · 1.72 Impact Factor
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    ABSTRACT: Cancer metastasis is refractory to most forms of chemotherapy. Conventional and alternative drugs, such as Chinese herbal remedies, have been developed to target metastatic cancer cells. In this study, we investigated the effects of PC-SPESII, an herbal formulation, on the migration, invasion, and metastasis of an experimental human breast cancer cell line in vivo and in vitro. PC-SPESII suppressed pulmonary metastasis and tumor growth of MDA-MB-231 human breast cancer xenografts without affecting body weight, liver function, and kidney function. PC-SPESII also inhibited MDA-MB-231 cell migration and invasion in vitro in a dose-dependent manner. Based on ELISA analysis, secretion of MMP-2 and MMP-9, proteins associated with extracellular matrix degradation, was reduced in response to PC-SPESII treatment. Western blot analysis of whole-cell extracts revealed that the levels of proteolytic proteins associated with matrix and base membrane degradation (MMP-2, MMP-9, and uPA) were decreased and the levels of their endogenous inhibitors (TIMP1 and TIMP2) were increased. Moreover, the p38MAPK and SAPK/JNK signaling pathway, which stimulates proteolytic enzymes and matrix degradation, was inhibited by PC-PSESII. Remarkably, cotreatment with PC-PSESII and p38MAPK or SAPK/JNK inhibitors magnified the antimetastatic phenotype. Our results indicate that PC-PSESII impairs human breast cancer metastasis by regulating proteolytic enzymes and matrix dynamics through the p38MAPK and SAPK/JNK pathway.
    Evidence-based Complementary and Alternative Medicine 01/2013; 2013:894386. · 1.72 Impact Factor
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    ABSTRACT: Traditional Chinese medicine (TCM) treatment is regarded as a safe and effective method for chronic hepatitis B (CHB), which requires a traditional diagnosis method to distinguish the TCM syndrome. In this study, we study the differences and similarities among excessive, excessive-deficient, and deficient syndromes, by an integrative and comparative analysis of weighted miRNA expression or miRNA-target network in CHB patients. We first calculated the differential expressed miRNAs based on random module t-test and classified three CHB TCM syndromes using SVM method. Then, miRNA target genes were obtained by validated database and predicted programs subsequently, the weighted miRNA-target networks were constructed for different TCM syndromes. Furthermore, prioritize target genes of networks of CHB TCM syndromes progression analyzed using DAVID online analysis. The results have shown that the difference between TCM syndromes is distinctly based on hierarchical cluster and network structure. GO and pathway analysis implicated that three CHB syndromes more likely have different molecular mechanisms, while the excessive-deficient and deficient syndromes are more dangerous than excessive syndrome in the process of tumorigenesis. This study suggested that miRNAs are important mediators for TCM syndromes classification as well as CHB development progression and therefore could be potential diagnosis and therapeutic molecular markers.
    Evidence-based Complementary and Alternative Medicine 01/2013; 2013:945245. · 1.72 Impact Factor
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    ABSTRACT: Herbal formulas based on the traditional Chinese medicine (TCM) syndrome (ZHENG) have been used as alternative treatments for breast cancer. However, there is a lack of the experimental animal ZHENG model for the evaluation of the herbal formulas. In this study, we have established 4T1 mouse breast cancer with Liver Fire Invading Stomach Syndrome model (4T1 LFISS mice) and investigated the effects of the herbal formula, Zuo-Jin Wan (ZJW). Our results showed that 4T1 LFISS mice have the features of LFISS including irritability, loss of appetite, yellow urine, chow, and a tail hot. Compared to untreated 4T1 LFISS mice, ZJW significantly reduced tumor weight and volume (P < 0.05), although it was weaker than Cisplatin. However, ZJW significantly increased the body weight and food intake of 4T1 LFISS mice and decreased serum ALT, AST, Cr, and BUN levels and ZHENG score (P < 0.05), while Cisplatin reduced the food intake, and body weight and increased serum ALT, AST, Cr, and BUN levels in 4T1 LFISS mice. Our study has provided a mouse breast cancer ZHENG model and showed that ZJW suppresses tumor growth and improves LFISS and kidney and liver functions in the 4T1 LFISS mice.
    Evidence-based Complementary and Alternative Medicine 01/2013; 2013:324732. · 1.72 Impact Factor
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    ABSTRACT: Cardiomyocytes apoptosis can lead to heart failure. Conventional and alternative drugs, such as Chinese herbal remedies, have been developed to target cardiomyoblast cells apoptosis. In this study, we investigated the effects of ginsenoside Rb1 (Rb1), an active compound, which is isolated from Notoginseng and Ginseng on isoproterenol-(ISO-) induced apoptosis in rat cardiomyocytes and its mechanism in vivo and in vitro. Rb1 reduced the ISO-induced apoptosis in rat cardiomyocytes and H9c2 cells. The effect of Rb1 was significantly suppressed by H89 (inhibitor for PKA), but not by C-1 (inhibitor for PKC). Based on in-cell blot analysis, the ISO-induced PKA and PKC expressions were decreased by Rb1, which was inhibited by H89, but not by C-1. The expressions of caspase-3 and caspase-9 were decreased after treatment with both ISO and Rb1, but with no change for caspase-8. Our results indicated that Rb1 reducing ISO-induced rat cardiomyocytes apoptosis may be involved in PKA and caspase-9 pathways.
    Evidence-based Complementary and Alternative Medicine 01/2013; 2013:454389. · 1.72 Impact Factor
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    ABSTRACT: To investigate the efficacy of mitomycin C (MMC) in combination with curcumin in suppressing human breast cancer in vitro and in vivo. Human breast cancer MCF-7 cells were used. Cell viability was measured using MTT assay. The cell cycle phase was detected with flow cytometric analysis. Cell cycle-associated proteins were examined using Western blot analysis. MCF-7 breast cancer xenografts were established to monitor tumor growth and cell cycle-associated protein expression. Curcumin inhibited MCF-7 breast cancer cell viability in a concentration-dependent manner (IC(50) value=40 μmol/L). Similarly, MMC inhibited the cell viability with an IC(50) value of 5 μmol/L. Combined treatment of MMC and curcumin showed a synergistic antiproliferative effect. In the presence of curcumin (40 μmol/L), the IC(50) value of MMC was reduced to 5 μmol/L. In MCF-7 xenografts, combined administration of curcumin (100 mg/kg) and MMC (1-2 mg/kg) for 4 weeks produced significantly greater inhibition on tumor growth than either treatment alone. The combined treatment resulted in significantly greater G(1) arrest than MMC or curcumin alone. Moreover, the cell cycle arrest was associated with inhibition of cyclin D1, cyclin E, cyclin A, cyclin-dependent kinase 2 (CDK2) and CDK4, along with the induction of the cell cycle inhibitor p21 and p27 both in MCF-7 cells and in MCF-7 xenografts. These proteins were regulated through p38 MAPK pathway. The results suggest that the combination of MMC and curcumin inhibits MCF-7 cell proliferation and cell cycle progression in vitro and in vivo via the p38 MAPK pathway.
    Acta Pharmacologica Sinica 11/2011; 32(11):1402-10. · 2.35 Impact Factor
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    ABSTRACT: Mitomycin C (MMC) potently suppresses tumour growth. However, its use is limited by its severe toxicity to the kidney and bone marrow. The purpose of this study is to investigate whether the chemoprevention agent curcumin can reduce MMC-associated side-effects and improve MMC efficacy in a breast cancer xenograft model. We first determined the effectiveness of combined MMC and curcumin to inhibit in vitro cell growth and to regress in vivo tumour outgrowth. We then investigated the mechanisms associated with MMC/curcumin-induced cell death by examining the effect of MMC/curcumin treatment on apoptosis, the activation of caspase-3, 8 and 9 and the expression of bcl-2 and bax. We also evaluated the ability of curcumin to alleviate MMC-associated side-effects by comparing the levels of creatinine/blood urea nitrogen (Cr/BUN) and glutamic oxalacetic transaminase/glutamic pyruvic transaminase (GPT/GOT) in serum between animals receiving MMC alone and MMC/curcumin. Curcumin significantly sensitised MCF-7 and MDA-MB-231 cells to MMC-induced cell death and improved MMC's ability to regress MCF-7 xenograft. MMC and curcumin together synergistically enhanced apoptosis in MCF-7 cells and the apoptosis most likely resulted from both the activation of caspases and modulation of bcl-2/bax expression. Most importantly, the inclusion of curcumin in MMC treatment decreased MMC-caused severe side-effects evidenced by significant improvement in the kidney function. Enhancing the tumoricidal effect of MMC, curcumin greatly reduces MMC-associated severe side-effects. Therefore, the combination treatment of MMC and curcumin may be of significant therapeutic benefit in treating breast cancer.
    European journal of cancer (Oxford, England: 1990) 05/2011; 47(14):2240-7. · 4.12 Impact Factor
  • Hui Zhang, Qian-Mei Zhou, Yi-Yu Lu, Jia Du, Shi-Bing Su
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    ABSTRACT: To investigate the effects of Aidi Injection on the MicroRNAs (miRNA) expression profiles in human breast cancer cells and explore the potential targets of the cancer treatment. MCF-7 breast cancer cells were grown in RPMI 1640 medium supplemented with different concentrations of ADI. The inhibition of cell proliferation was measured by MTT assay. MCF-7 cells were treated by ADI with above 50% inhibiting concentration (IC50) for 48 h. The expression profiles of miRNA in ADI-treated and ADI-untreated MCF-7 cells were detected with miRNA microarray chips and the array data were verified by quantitative RT-PCR. MCF-7 cells were transiently transfected with miRNA mimics by liposome method. Potential mRNA targets were predicted by informatics analysis with TargetScan and PicTar software. ADI significantly inhibited the proliferation of MCF-7 cells in a dose-dependent manner. The IC50 of ADI was 55.71 mg/mL after treatment for 48 h. The 60 mg/mL ADI was used as the therapeutic drug concentration. Microarray analysis identified 45 miRNAs that were up-regulated and 55 miRNAs that were down-regulated in response to ADI treatment. Many ADI-induced miRNAs were related to breast cancers. The microarray data were validated by qRT-PCR. Ectopic expression of 100 nmol/L mir-126 mimics significantly inhibited the proliferation of MCF-7 cells. The 12 potential target genes of mir-126 were predicted by both TargetScan and PicTar software. The miRNA may serve as therapeutic targets, and the modulation of miRNA expression is an important mechanism of ADI inhibiting breast cancer cell growth.
    Journal of Traditional Chinese Medicine 03/2011; 31(1):10-6. · 0.59 Impact Factor
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    ABSTRACT: To examine whether the cell growth inhibitory effect of the combination of baicalin and baicalein is related to apoptosis. Moreover, to determine whether the expression of some apoptosis-related proteins is regulated by the ERK/p38 MAPK pathway. Cell viability was measured using a 3-(4,5-dimethylthiazol-2-yl)-2, 5-diphenyltetrazolium bromide (MTT) assay. Apoptosis was detected by acridine orange (AO) staining, DNA ladder assay and flow cytometric analysis. Apoptosis-related proteins were observed using Western blot analysis. Compared with baicalin or baicalein alone, the combination treatment of baicalin (50 micromol/L) and baicalein (25 micromol/L) had an anti-proliferative effect in a time-dependent manner. Isobologram analysis demonstrated that the combination treatment had a synergistic effect. Moreover, apoptosis in MCF-7 cells was increased by 12% and 20% with the combination treatment at 24 h and 48 h, respectively. With the combination treatment in MCF-7 cells, cleaved caspase-3 and caspase-9 were observed, and the level of bcl-2 expression was decreased approximately 20% and 40% at 24 h and 48 h, respectively. The expression of bax and p53 were increased about 25% and 15% at 48 h, respectively. Moreover, the activation of caspase-3, -9 and the regulation of bcl-2, bax and p53 were related to ERK /p38 MAPK activation. In this study, apoptosis was enhanced by the combination treatment of baicalin and baicalein, which activated caspases-3 and caspase-9, downregulated the level of bcl-2 and upregulated the level of bax or p53 via the ERK/p38 MAPK pathway.
    Acta Pharmacologica Sinica 12/2009; 30(12):1648-58. · 2.35 Impact Factor
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    ABSTRACT: Mitomycin C (MMC), a chemotherapeutic agent in breast cancer treatments, inhibits tumor growth through DNA cross-linking and breaking, but it has severe side effects. Here we examined whether and how curcumin reduced the side effects of MMC. We found that combination treatment with MMC and curcumin reduced tumor weight by 70% and 36% compared with saline and curcumin-treated groups, respectively. The combination treatment reduced weight loss and improved kidney function and bone marrow suppression compared with MMC treatment alone. Moreover, the combination treatment inhibited glucose regulatory protein (GRP58)-mediated DNA cross-linking. The combination treatment inhibited GRP58 through the ERK/p38 MAPK pathway. In conclusion, the current study provided evidence that MMC and curcumin combination treatment reduced MMC side effects by inhibiting GRP58-mediated DNA cross-linking through the ERK/p38 MAPK pathway.
    Cancer Science 08/2009; 100(11):2040-5. · 3.48 Impact Factor
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    Hui Zhang, Shi-Bing Su, Qian-Mei Zhou, Yi-Yu Lu
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    ABSTRACT: Aberrant expression of microRNAs (miRNAs) is involved in the development of breast cancer. This study was to explore differential expression of miRNAs between breast cancer cells and mammary epithelial cells, and to predict potential targets of the differentially expressed miRNAs. Human breast cancer MCF-7 cells and normal human mammary epithelial HBL-100 cells were cultured. The total RNA was isolated and examined. The expression profiles of miRNAs in MCF-7 and HBL-100 cells were detected with a miRNA microarray chip and compared. Array results were confirmed by real-time polymerase chain reaction (PCR). Potential mRNA targets were predicted by MiRanda, TargetScan, PicTar, and DIANA-microT software. The purification of total RNA from MCF-7 and HBL-100 cells was relatively high. According to a microarray-based screening, 173 breast cancer-related miRNAs were identified. Of the 173 miRNAs, 113 were up-regulated and 60 were down-regulated in MCF-7 cells (P<0.01). Real-time PCR showed that mir-18a and mir-195 were highly expressed in MCF-7 cells. Sixty-eight potential target genes of mir-200b were predicted by informatics analysis. The miRNA expression profiles of breast cancer cells and mammary epithelial cells are obtained. Some miRNAs may be involved in the pathogenesis of breast cancer by regulating their target genes.
    Ai zheng = Aizheng = Chinese journal of cancer 06/2009; 28(5):493-9.
  • Qian-Mei Zhou, Shi-Bing Su, Hui Zhang, Yi-Yu Lu
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    ABSTRACT: To observe the effect of curcumin on protein kinases on cell signal pathway in breast cancer cell MCF-7. The suppressive effect of curcumin on MCF-7 cell proliferation as different concentration and at different time points were observed by MTT assay; The activity of p-ERK, p-NF-kappaB, p-p38 and p-JNK were observed by western blot. The suppressive effect of curcumin was shown as a dose dependent and a time dependent manner,and the IC50 was 22.48 micromol/L 40 micromol/L curcumin inhibited the expression of p-ERK, p-NF-kappaB and p-p38, but not p-JNK. Curcumin can inhibit MCF-7 cell's proliferation, and its mechanism may be related to the activities of protein kinases on cell signal pathway.
    Zhong yao cai = Zhongyaocai = Journal of Chinese medicinal materials 05/2009; 32(5):728-32.
  • Qian-Mei Zhou, Shi-Bing Su
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    ABSTRACT: A review was about the mechanism of Chinese herbal medicine and its compounds intervening breast cancer in recent years. Experimental results showed that Chinese herbal medicine and its compounds have the activity of anti-cancer, through inhibiting the growth and proliferation of breast cancer cells, restraining the metastasis, appearing the estrogen-like activity and improving multi-drug resistance, and so on.
    Zhongguo Zhong yao za zhi = Zhongguo zhongyao zazhi = China journal of Chinese materia medica 10/2007; 32(18):1947-50.