血管内皮细胞通过诱导ERG表达促进前列腺癌耐药

目的:探讨血管内皮细胞对前列腺癌细胞耐药能力的影响,并进一步研究血管内皮细胞作用于前列腺癌细胞的可能的分子机制。方法:1.利用Transwell小室构建共培养体系,通过CCK-8和Annexin V-FITC/PI检测细胞耐药的能力并通过蛋白印迹法(WB)检测凋亡相关分子的表达;2.利用聚合酶链式反应(PCR)及WB检测共培养后前列腺癌细胞中成红细胞病毒E26致癌物(ERG)的表达情况;利用酶联免疫吸附实验(ELISA)筛选出共培养组与非共培养组细胞上清之间有差异的细胞因子,并通过WB检测各个细胞因子与ERG的关系,确定影响ERG表达最明显的细胞因子。结果:1.前列腺癌细胞与血管内皮细胞共培养后,前列腺癌细胞对多西他赛的耐药性增加,细胞凋亡减少;2.共培养后前列腺癌细胞ERG的表达增高;血管内皮细胞分泌的成纤维细胞生长因子2(FGF2)在共培养后有明显增加,FGF2可以促进前列腺癌ERG的表达,并且这种病效应会被FGF2的抑制剂所逆转。结论:血管内皮细胞分泌的FGF2可促进前列腺癌细胞ERG的表达,促进前列腺癌细胞对多西他赛的耐药性。

Endothelial Cells Promote Prostate Cancer Resistance by Inducing ERG Expression

ABSTRACT Objective: To investigate the effect of endothelial cells on drug resistance of prostate cancer cells and to further study the possible molecular mechanism of endothelial cells acting on prostate cancer cells. Methods: 1. The co-culture system was constructed by Transwell chamber. the drug resistance of cells was detected by CCK-8 and Annexin V-FITC/PI, and the expression of apoptosis-related molecules was detected by western blotting (WB). 2. Polymerase Chain Reaction (PCR) and WB were used to detect the expression of erythroblastosis virus E26 oncogen (ERG) in prostate cancer cells after co-culture. The cytokines in the supernatant of co-culture group and non-co-culture group were screened by ELISA, and the relationship between each cytokine and ERG was detected by WB to determine the most obvious cytokines affecting the expression of ERG. Results: 1. After co-culture of prostate cancer cells and endothelial cells, the resistance of prostate cancer cells to docetaxel increased and apoptosis decreased. 2. The expression of ERG in prostate cancer cells was increased after co-culture. Fibroblast growth factor 2(FGF2) secreted by vascular endothelial cells increased significantly after co-culture. FGF2 can promote the expression of ERG in prostate cancer, and this effect will be reversed by the inhibitor of FGF2. Conclusion: FGF2 secreted by vascular endothelial cells can promote the expression of ERG in prostate cancer cells and promote the resistance of prostate cancer cells to docetaxel.