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论文摘要

银杏酚酸提高Tca8113 对化学治疗药物敏感性的研究

Ginkgolic acids can enhance the drug-sensitivity of Tca8113

作者:戴丽娜 苏勤 周陈晨 王辉 陈娇 张平

Author:DAI Li-na, SU Qin, ZHOU Chen-chen, WANG Hui, CHEN Jiao, ZHANG Ping.

收稿日期:2010-08-31          年卷(期)页码:2011,38(3):268-273

期刊名称:国际口腔医学杂志

Journal Name:International Journal of Stomatology

关键字:程序性细胞死亡, 蛋白质激酶D,银杏酚酸, Tca8113, 细胞增殖,

Key words:ginkgolic acid, Tca8113, cell proliferation, programmed cell death, protein kinase D,

基金项目:

中文摘要

目的探讨银杏酚酸(GA)提高舌鳞状细胞癌Tca8113 对化疗药物的敏感性及其机制。方法以甲噻唑 四唑氮(MTT)检测单独用药与联合用药时Tca8113 的生存率,蛋白质印迹技术检测不同作用时间GA 对Tca8113 中蛋白质激酶D(PkD)-2的表达和对其磷酸化的影响,利用shRNA 干扰技术沉默Tca8113 中pkD-2 基因,分别 用MTT 和流式细胞术分析转染前后细胞的生长和程序性死亡。结果GA 可明显提高Tca8113 对卡铂和紫杉醇 的敏感性;与非磷酸化PkD-2 蛋白质表达相比较,GA 对Tca8113 中磷酸化PkD-2 蛋白质的表达呈时间依赖性 抑制作用;shRNA 技术干扰后的Tca8113 与对照组细胞相比较,癌细胞内pkD-2 mRNA 及其蛋白质表达均下 降,癌细胞增殖率明显下降,癌细胞对化疗药物诱导的程序性细胞死亡率增高。结论GA 可能通过抑制PkD-2 蛋白质磷酸化途径诱导Tca8113 程序性死亡,增加癌细胞对化疗药物的敏感性。

英文摘要

Objective To investigate the effect and mechanism of ginkgolic acid(GA) on drug -sensitivity of Tca8113 cells to chemotherapy drug. Methods Methyl thiazolyl tetrazolium(MTT) assay for detection of single use of Carboplatin(CBP) or Paclitaxel(PTX) and combination of CBP or PTX with GA on Tca8113 cell survival rate. Western blot detection of protein expression of p-protein kinase D(PkD)-2 and PkD-2 in Tca8113 cell induced by GA with different times, shRNA was introduced to downregulate the expression of PkD-2 in Tca8113 cell line. The proliferation activity and programmed cell death rate of shRNA mediated Tca8113 cells were detected by MTT and flow cytometry respectively. Results The drug-sensitivity of Tca8113 cells was enhanced by GA significantly; the expression of p-PkD-2 protein in Tca8113 cells was inhibited by GA in a time-dependent manner vs PkD-2, compared to the control, shRNA targeting of PkD-2 leads to the efficient and specific silence of pkD-2 mRNA and protein expression as determined by RT-PCR and Western blot, a dramatic reduction of cell proliferation and an increased programmed cell death rate of Tca8113 cells treated with chemotherapy drug in vitro. Conclusion GA can induce Tca8113 cells programmed cell death by inhibiting the phosphorylation of p- PkD-2,thus enhance the sensitivity of Tca8113 cells to chemotherapy drug.

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