Quan Fang, Pan Chengen, Ma Qingyong, Zhang Shaoqiang, Yan Liying
Department of ENT & Head and Neck Surgery, The First Affiliated Hospital, Medical College of Xi'an Jiaotong University, No. 277 West Yanta Road, Xi'an 710061, PR China.
Biomed Pharmacother. 2008 Nov;62(9):622-9. doi: 10.1016/j.biopha.2008.07.089. Epub 2008 Aug 28.
A multidrug-resistant clone of human oral epidermoid carcinoma KB cells was isolated by stepwise selection on exposure to increasing doses of vincristine. The final clone, KBv200, obtained after ethylmethane sulfonate mutagenesis showed 156-fold higher resistance to vincristine than KB cells. The cells were also cross-resistant to paclitaxel and adriamycin. The aim of this study was to explore the reversal effect and potential mechanism of resveratrol on KBv200 cells. MTT assay was used to investigate the reversal index of resveratrol to vincristine, adriamycin and paclitaxel. Cell apoptosis was measured by flow cytometry. RT-PCR and western blot were used to detect mRNA and protein expression of multidrug-resistant gene MDR1 and apoptosis-suppressing gene Bcl-2. Resveratrol produced a synergistic effect combined with the chemotherapeutic agents and reversed the multidrug-resistant phenotype of KBv200 cells. Flow cytometry confirmed that the percentage of apoptotic cell increased when KBv200 cells were exposed to resveratrol. The results of gene detection showed that the expression levels of MDR1 and Bcl-2 were decreased upon resveratrol treatment. Resveratrol can efficiently reverse multidrug resistance in KBv200 cells. The potential mechanism may be via inhibiting the multidrug-resistant gene expressions and/or promoting cell apoptosis.
通过逐步增加长春新碱剂量进行筛选，分离出一株人口腔表皮样癌KB细胞的多药耐药克隆。经甲磺酸乙酯诱变后获得的最终克隆KBv200，对长春新碱的耐药性比KB细胞高156倍。这些细胞对紫杉醇和阿霉素也具有交叉耐药性。本研究的目的是探讨白藜芦醇对KBv200细胞的逆转作用及其潜在机制。采用MTT法研究白藜芦醇对长春新碱、阿霉素和紫杉醇的逆转指数。通过流式细胞术检测细胞凋亡。采用RT-PCR和蛋白质印迹法检测多药耐药基因MDR1和凋亡抑制基因Bcl-2的mRNA和蛋白表达。白藜芦醇与化疗药物联合产生协同作用，逆转了KBv200细胞的多药耐药表型。流式细胞术证实，KBv200细胞暴露于白藜芦醇时凋亡细胞百分比增加。基因检测结果显示，白藜芦醇处理后MDR1和Bcl-2的表达水平降低。白藜芦醇可有效逆转KBv200细胞的多药耐药性。其潜在机制可能是通过抑制多药耐药基因表达和/或促进细胞凋亡。
