Jaworska Dagmara, Szliszka Ewelina
Department of Microbiology and Immunology, School of Medicine with the Division of Dentistry in Zabrze, Medical University of Silesia in Katowice, Jordana 19, 41-808 Zabrze, Poland.
Int J Mol Sci. 2017 Jul 29;18(8):1648. doi: 10.3390/ijms18081648.
Numerous data suggest that an increase of cancer stem cells (CSCs) in tumor mass can be the reason for failure of conventional therapies because of their resistance. CD44+/CD24- cells are a putative cancer stem cells subpopulation in prostate cancer. TRAIL (tumor necrosis factor-related apoptosis-inducing ligand) is an activator of apoptosis in tumor cells. However, some tumors are TRAIL-resistant. Cancer cells can be re-sensitized to TRAIL induced apoptosis by a combination of TRAIL and taxanes. The aim of this work was to analyze the enhancement of the anticancer effect of TRAIL by paclitaxel, cabazitaxel and docetaxel in the whole population of PC3 and DU145 prostate cancer cells, but also in CD44+/CD24- prostate cancer stem cells. We examined the apoptotic effect of TRAIL and taxanes using flow cytometry and Annexin-V-PE staining. The co-treatment with taxanes and TRAIL enhanced significantly the apoptosis in CD44+/CD24- cells only in PC3 cell line but not in DU145 cells. We discovered also that taxanes can increase the expression of death receptor TRAIL-R2 in PC3 prostate cancer cells. The results of our study show that treatment with paclitaxel, cabazitaxel and docetaxel is able to enhance the apoptosis induced by TRAIL even in prostate cancer stem cells.
大量数据表明，肿瘤块中癌症干细胞（CSCs）的增加可能是传统疗法失败的原因，因为它们具有抗性。CD44+/CD24-细胞是前列腺癌中一种假定的癌症干细胞亚群。TRAIL（肿瘤坏死因子相关凋亡诱导配体）是肿瘤细胞凋亡的激活剂。然而，一些肿瘤对TRAIL具有抗性。通过TRAIL与紫杉烷类药物联合使用，癌细胞可重新对TRAIL诱导的凋亡敏感。这项工作的目的是分析紫杉醇、卡巴他赛和多西他赛在整个PC3和DU145前列腺癌细胞群体中，以及在CD44+/CD24-前列腺癌干细胞中对TRAIL抗癌作用的增强效果。我们使用流式细胞术和膜联蛋白-V-PE染色检测了TRAIL和紫杉烷类药物的凋亡作用。紫杉烷类药物与TRAIL联合处理仅在PC3细胞系中显著增强了CD44+/CD24-细胞的凋亡，而在DU145细胞中未增强。我们还发现紫杉烷类药物可增加PC3前列腺癌细胞中死亡受体TRAIL-R2的表达。我们的研究结果表明，紫杉醇、卡巴他赛和多西他赛治疗即使在前列腺癌干细胞中也能够增强TRAIL诱导的凋亡。
