[show abstract][hide abstract] ABSTRACT: miRNA-22 was previously reported to be a tumor suppressor. The aim of this study was to explore the expression and function of miRNA-22 in esophageal squamous cell carcinoma (ESCC). Expression of miRNA-22 in 100 ESCC tissues was examined by q-PCR. The correlation between miRNA-22 level and clinicopathological features was analyzed using SPSS16.0 statistical software. Moreover, the effect of miRNA-22 expression on radiosensitivity of ESCC cells was examined. miRNA-22 expression decreased in ESCC tissues, and statistical analyses showed that the expression of miRNA-22 was associated with the stage of clinical classification. No correlation was found between miRNA-22 expression and the overall survival of ESCC patients. However, significant positive correlation was found between miRNA-22 expression and the survival of patients who received radiotherapy (P < 0.05). Increased expression of miRNA-22 sensitized ESCC cells to γ-ray radiation and promoted the apoptosis of ESCC cells induced by γ-ray radiation. Increased expression level of miRNA-22 had effects on Rad51 expression after irradiation. These results demonstrate for the first time that decreased miRNA-22 expression correlates with increased radiotherapy resistance of ESCC, and that this effect is mediated, at least in part, by the Rad51 pathway.
Journal of Radiation Research 11/2012; · 1.45 Impact Factor
[show abstract][hide abstract] ABSTRACT: To appraise the efficacy of Vam3 (Amurensis H), a dimeric derivative of resveratrol, at inhibiting cigarette smoke-induced autophagy.
Human bronchial epithelial cells were treated with cigarette smoke condensates, and a chronic obstructive pulmonary disease (COPD) model was established by exposing male BALB/c mice to cigarette smoke. The protein levels of the autophagic marker microtubule-associated protein 1A/1B-light chain 3 (LC3), Sirtuin 1 (Sirt1), and foxhead box O 3a (FoxO3a) were examined using Western blotting and Immunohistochemistry. LC3 punctae were detected by immunofluorescence. The levels of FoxO3a acetylation were examined by immunoprecipitation. The level of intracellular oxidation was assessed by detecting ROS and GSH-Px.
Vam3 attenuated cigarette smoke condensate-induced autophagy in human bronchial epithelial cells, and restored the expression levels of Sirt1 and FoxO3a that had been reduced by cigarette smoke condensates. Similar protective effects of Vam3, reducing autophagy and restoring the levels of Sirt1 and FoxO3a, were observed in the COPD animal model. Additionally, Vam3 also diminished the oxidative stress that was induced by the cigarette smoke condensates.
Vam3 decreases cigarette smoke-induced autophagy via up-regulating/restoring the levels of Sirt1 and FoxO3a and inhibiting the induced oxidative stress.
[show abstract][hide abstract] ABSTRACT: Currently, about 300 million people worldwide are affected by asthma. Most of these sufferers inhale immunosuppressants (ie corticosteroids) and beta-adrenergic receptor agonists for their asthma treatment. However, about 5%-10% of patients of asthma have poor response to such treatment. Investigation of kinase signaling pathway and nuclear transcription factor as a target molecule in the treatment of allergic asthma has been the concern of scholars home and abroad. This paper reviewed inhibitors of kinase signaling pathway and nuclear transcription factors for the treatment of asthma.
Yao xue xue bao = Acta pharmaceutica Sinica 06/2012; 47(6):689-95.
[show abstract][hide abstract] ABSTRACT: Sirtuin1 (Sirt1) is a NAD-dependent class III histone deacetylase (HDAC), and regulates pulmonary immune/inflammatory system and the aging process mainly through post-translational modification. Sirt1 could become a potential target for treatment of lung diseases due to participating in the development of a variety of lung diseases. In this paper, physiological characteristics, biological activities, modification regulations and its relationship with chronic obstructive pulmonary emphysema, asthma and lung cancer are reviewed.
Yao xue xue bao = Acta pharmaceutica Sinica 04/2012; 47(4):417-20.
[show abstract][hide abstract] ABSTRACT: We performed the study to investigate whether adenovirus-mediated retinoblastoma 94 (RB94) gene transfer could enhance radiation treatment of esophageal squamous cell carcinoma (ESCC) in vitro and in vivo. ESCC cells (Kyse150 cell line) were cultivated in vitro and tumors originated from the cell line were propagated as xenografts in nude mice. Treatment with Ad-RB94 and/or ionizing radiation (IR) was carried out both in vitro and in vivo with Ad-LacZ control vector and blank control. Cell viability, cell cycle distribution, cell apoptosis, tumor growth and transfected gene expression were evaluated and tumor degeneration was analyzed. The data of quantification real-time PCR assays and immunohistochemistry staining using RB antibody indicated that RB94 was efficiently transfected into Kyse150 cells. In vitro, data of cell growth assay indicated that treatment with Ad-RB94 improved radiation treatment of Kyse150 cells. Tumor xenograft studies, pathological analysis of H.E. staining and Ki67 staining suggested transfecting RB94 enhanced tumor regression induced by radiation treatment in vivo. In addition, data of Annexin V, TUNEL and cell cycle distribution assays proposed combination treatment effectively induced cell apoptosis and cell cycle arresting in G2/M phase. In conclusion, transferring RB94 gene by the adenoviral vector enhances radiation treatment of ESCC.
Journal of Radiation Research 01/2012; 53(1):117-24. · 1.45 Impact Factor
[show abstract][hide abstract] ABSTRACT: The Cks1 protein is a member of the highly conserved family of Cks/Suc1 proteins, which interact with Cdks, and was found to be an essential cofactor for efficient Skp2-dependent ubiquitination of p27. The present study was undertaken to examine the expression status of Cks1 in esophageal squamous cell carcinoma and its significance.
The expression of Cks1 in 140 esophageal squamous cell carcinoma patients was examined by immunohistochemistry. The correlations between Cks1 expression and tumor clinicopathologic features were analyzed. The effects of Cks1 expression on radiotherapy results were also examined.
In the present study, we found that Cks1 is overexpressed in esophageal squamous cell carcinoma tissues. Elevated expression of Cks1 correlates significantly with tumor stage and positive lymph node metastasis (p < 0.05). Moreover, a significant negative correlation was found between Cks1 expression and the survival of patients who received radiotherapy (p < 0.05). At the molecular level, forced expression of Cks1 promotes the radio-resistance ability of EC9706 cells. Knockdown of Cks1 expression sensitizes cancer cells to radiation, and a wobble mutant of Cks1 that is resistant to Cks1 siRNA can rescue this effect.
These results demonstrate for the first time that overexpression of Cks1 correlates with the increased radiotherapy resistance of esophageal squamous cell carcinoma.
Journal of Radiation Research 01/2012; 53(1):72-8. · 1.45 Impact Factor
[show abstract][hide abstract] ABSTRACT: miRNAs are small, non-coding RNAs that negatively regulate gene expression at the post-transcriptional and translational levels. miRNA-451 was previously reported to be down-regulated in gastric and colorectal cancers. Here, we showed that miRNA-451 expression decreased in non-small cell lung cancer (NSCLC) tissues and that its expression was negatively associated with lymph node metastasis, the stage of TNM classification and poor prognosis of NSCLC patients. Moreover, significantly different miRNA-451 expression levels were found between smoking and non-smoking patients. The overexpression of miRNA-451 inhibited cell cycle progression, cellular migration and the invasive ability of NSCLC cells. Increased miRNA-451 expression also promoted anoikis of NSCLC cells. Together, these data suggested that aberrantly expressed miRNA-451 may be associated with the development of NSCLC.
Cancer letters 08/2011; 311(2):203-9. · 4.86 Impact Factor
[show abstract][hide abstract] ABSTRACT: This study is to investigate the protective effects of the SB203580 against radiation induced mortality and intestinal injury of mice. A total of 67 male C57BL/6 mice (20.0-22.0 g) were matched according to body weight and randomly assigned to one of three groups: control, total body irradiation exposure (IR, 7.2 Gy) only, and IR (7.2 Gy) + SB203580 (15 mg x kg(-1)). 30 days survival rate was observed in the experiment. In intestinal injury experiment, the expression levels of caspase-3, Ki67, p53 and p-p38 were assayed in the mice intestine crypts. The results showed that the 30 days survival rate was 100% (control), 0 (IR) and 40% (IR+ SB203580), separately. Compared to the IR groups, the positive cells of caspase-3, p53 and p-p38 in crypt cells decreased 33.00%, 21.78% and 34.63%, respectively. The rate of positive cells of Ki67 increased 37.96%. Significant difference was found between all of them (P < 0.01). SB203580 potently protected against radiation-induced lethal and intestinal injury in mice, and it may be a potential radio protector.
Yao xue xue bao = Acta pharmaceutica Sinica 04/2011; 46(4):395-9.
[show abstract][hide abstract] ABSTRACT: To investigate the different miRNA expression profiles of postoperative radiotherapy sensitive and resistant patients of non-small cell lung cancer, explore their potential role and find some radio-sensitivity markers.
Thirty non-small cell lung cancer patients who have been treated by postoperative radiotherapy were selected and were divided into radiotherapy sensitive group and resistant group according to overall survival and local or distant recurrence rate. Expression profile of miRNA in these two groups was detected by a microarray assay and the results were validated by quantitative RT-PCR and Northern blot. At the molecular level, the effect of one differently expressed miRNA (miR-126) on the growth and apoptosis of SK-MES-1 cells induced by irradiation was examined.
Comparing with resistant patients, five miRNAs (miRNA-126, miRNA-let-7a, miRNA-495, miRNA-451 and miRNA-128b) were significantly upregulated and seven miRNAs (miRNA-130a, miRNA-106b, miRNA-19b, miRNA-22, miRNA-15b, miRNA-17-5p and miRNA-21) were greatly downregulated in radiotherapy sensitive group. Overexpression of miRNA-126 inhibited the growth of SK-MES-1 cells and promoted its apoptosis induced by irradiation. The expression level of p-Akt decreased in miRNA-126 overexpression group. After treating with phosphoinositidyl-3 kinase (PI3K) constitutively activator (IGF-1) and inhibitor (LY294002), miRNA-126 overexpression had no significant effects on the apoptosis of SK-MES-1 cells.
We found 12 differently expressed miRNAs in the radiotherapy sensitive and resistant non-small cell lung cancer samples. Moreover, our results showed miRNA-126 promoted non-small cell lung cancer cells apoptosis induced by irradiation through the PI3K-Akt pathway.
Lung cancer (Amsterdam, Netherlands) 04/2011; 72(1):92-9. · 3.14 Impact Factor
[show abstract][hide abstract] ABSTRACT: MicroRNAs are short regulatory RNAs that negatively modulate gene expression at the posttranscriptional level and are deeply involved in the pathogenesis of several types of cancer. The miRNA-130a has been shown to play a role in antagonizing the inhibitory effects of GAX on endothelial cell proliferation, migration and tube formation, and antagonizing the inhibitory effects of HoxA5 on tube formation in vitro. Here the authors show, for the first time, that miRNA-130a expression is increased in nonsmall cell lung cancer (NSCLC) tissues. Statistical analysis showed that overexpression of miRNA-130a was strongly associated with lymph node metastasis, stage of tumor node metastasis classification and poor prognosis. Moreover, there was a significant difference in miRNA-130a expression levels between smoking and nonsmoking patients. Multivariate Cox regression analysis showed that miRNA-130a was an independent prognostic factor for patients with NSCLC. Together, these data suggest that miRNA-130a may comprise a potential novel prognostic marker for this disease.
The American Journal of the Medical Sciences 11/2010; 340(5):385-8. · 1.33 Impact Factor
[show abstract][hide abstract] ABSTRACT: Gold nanoparticles have potential applications in biomedicine, but one of the important concerns is about their safety. Most toxicology data are derived from in vitro studies and may not reflect in vivo responses. Here, an animal toxicity study of 13.5 nm gold nanoparticles in mice is presented. Animal survival, weight, hematology, morphology, and organ index are characterized at different concentrations (137.5-2200 μg/kg) over 14-28 days. The results show that low concentrations of gold nanoparticles do not cause an obvious decrease in body weight or appreciable toxicity, even after their breakdown in vivo. High concentrations of gold nanoparticles induced decreases in body weight, red blood cells, and hematocrit. It was also found that gold nanoparticles administered orally caused significant decreases in body weight, spleen index, and red blood cells. Of the three administration routes, the oral and intraperitoneal routes showed the highest toxicity, and the tail vein injection showed the lowest toxicity. Combining the results of all of these studies, we suggest that targeted gold nanopartices by tail vein injection may be suitable for enhancement of radiotherapy, photothermal therapy, and related medical diagnostic procedures.
International Journal of Nanomedicine 01/2010; 5:771-81. · 3.46 Impact Factor
[show abstract][hide abstract] ABSTRACT: The present study was undertaken to examine the amplification and expression status of Cks1 in breast cancer and its significance.
The amplification and expression status of Cks1 gene was examined by FISH, real-time PCR and immunohistochemistry, respectively. RNA interference was used to detect the effects of Cks1 on migration, invasion, cell cycle progress and apoptosis of breast cancer cells.
Cks1 gene amplification was highly correlated with protein overexpression. Overexpression of Cks1 was strongly associated with lymph node metastasis and poor prognosis (P = 0.000, 95% CI (0.00-0.02); P = 0.008, 95% CI (0.001-0.05), respectively). Knockdown of Cks1 expression by RNA interference inhibited the cell cycle progress, migration and invasion ability of breast cancer cells. Moreover, overexpression of Cks1 inhibited apoptosis of breast cancer cells through MEK-Erk pathway.
Cks1 may be considered as potential novel prognostic markers and targets for the future development of specific therapeutic interventions in breast cancer.
Journal of Cancer Research and Clinical Oncology 05/2009; 135(10):1393-401. · 2.91 Impact Factor
[show abstract][hide abstract] ABSTRACT: Gain of chromosome 1q is a common event in many kinds of carcinomas. The Cks1 gene, located at 1q21, is required for p27 ubiquitination by the SCF(skp2) ubiquitinating machinery. In the present study, we found that Cks1 gene amplification was highly correlated with protein overexpression. Statistical analysis showed that amplification and overexpression of Cks1 were strongly associated with lymph node metastasis and poor prognosis. At the molecular level, knockdown of Cks1 expression by RNA interference inhibited the growth of MDA-MB-231 cells, damaged cell migration and invasion ability. Knockdown of Cks1 expression promoted apoptosis of breast cancer cells and a wobble mutant of Cks1 that was resistant to Cks1 siRNA can rescue this effect. Overexpression of Cks1 inhibited the apoptosis of breast cancer cells through the MEK-Erk pathway. These data suggest that Cks1 is an oncogene in the 1q21 amplicon and plays an important role for breast cancer development.
Biochemical and Biophysical Research Communications 02/2009; 379(4):1107-13. · 2.41 Impact Factor