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多西紫杉醇诱导前列腺癌细胞耐药的Cofflin-1蛋白通路机制研究

he effect of docetaxel induces apoptosis of prostate cancer cells through cofilin-1 and paxillin signal pathway

中文摘要英文摘要

前列腺癌是欧美地区男性最常见的恶性肿瘤,在我国的发病率也有逐渐增高的趋势。由于前列腺癌早期发病隐蔽,多数患者发现时已有骨转移,失去手术机会,而长期应用抗雄激素治疗,则使激素依赖性前列腺癌逐渐转变为激素非依赖性前列腺癌,预后不良。紫杉醇是近年来应用于激素非依赖性前列腺癌的一种有效的化疗药物,其对前列腺癌具有诱导凋亡作用,但耐药性的出现使其治疗效果大打折扣。本研究对多西紫杉醇通过Cofilin-1及paxillin 通路在诱导前列腺癌细胞凋亡中的作用机制进行了研究,为前列腺癌的临床治疗打下了一定的基础。目的:对多西紫杉醇通过Cofilin-1及paxillin 通路在诱导前列腺癌细胞凋亡中的作用机制进行研究,为前列腺癌的临床治疗打下一定的基础。方法:不同浓度的多西紫杉醇(1-50nM)作用于前列腺癌细胞系(LNCaP)24小时。分别通过MMT法及乳酸脱氢酶法测量细胞生长率及细胞毒性,应用流式细胞仪及半胱天冬酶3途径测量紫杉醇诱导的细胞死亡,同时应用RT-PCR测量Cofilin-1基因的表达,应用免疫印迹法探测桩蛋白的表达。结果:多西紫杉醇对前列腺癌细胞的生长有抑制作用,并增加细胞毒性,激活细胞的凋亡,促进LNCaP细胞内半胱天冬酶3的活性。同时发现多西紫杉醇降低了LNCaP细胞中Cofilin-1基因的表达以及桩蛋白的表达,而将Cofilin-1基因剔除后,可通过抑制桩蛋白通路而加强多西紫杉醇的抗肿瘤效果。结论:多西紫杉醇通过抑制Cofilin-1基因和桩蛋白的表达途径来诱导细胞凋亡,发挥其抗肿瘤的作用。

Prostate cancer is a common multiple malignant tumor of male, whose mortality is the 2nd highest of all kinds of tumours in western countries, and the mortality of morbidity is 13% in the USA. The objective of this study was performed to investigate the anti-cancer effect of docetaxel induces apoptosis of prostate cancer through cofilin-1 and paxillin signal path. Treatment docetaxel (1-50 nM) disposed the human prostate cancer (LNCaP) cells for 24 h. Then cell growth and cytotoxicity were measured using 3-(4,5-dimethylthiazol-2-yl)-2,5 -diphenyltetrazolium bromide assay (MTT) and Lactate dehydrogenase (LDH) assay, respectively. Docetaxel-induced cell death was analyzed using Flow cytometric and Caspase-3 assay, respectively. Real-time RT-PCR analysis was used to detect the expression of cofilin-1 gene and western blots was also used to probe the protein expression of paxillin. We found that supplement with docetaxel could inhibit cell growth, promoted cytotoxicity, activated apoptosis and increased caspase-3 activity in LNCaP cell. Interesting, administrate of docetaxel reduced the expression of cofilin-1 gene and the protein expression of paxillin in LNCaP cell. Meanwhile, knockdown of cofilin-1 advanced the anti-cancer effect of docetaxel against LNCaP cell through suppression of paxillin pathway. The present findings that the anti-cancer effect of docetaxel induces apoptosis of prostate cancer through suppression of cofilin-1 and paxillin signal path, and which will help to set a stage to the clinical treatment of prostate cancer.

萧畔、张怀强

肿瘤学基础医学药学

外科学多西紫杉醇前列腺癌ofilin-1Paxillin

docetaxel prostate cancer cofilin-1 paxillin

萧畔,张怀强.多西紫杉醇诱导前列腺癌细胞耐药的Cofflin-1蛋白通路机制研究[EB/OL].(2017-04-24)[2025-08-18].http://www.paper.edu.cn/releasepaper/content/201704-390.点此复制

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