癌相关成纤维细胞对上皮性卵巢癌细胞耐药性影响及机制初步研究
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江苏省妇幼保健科研项目(F201438)


Effects and mechanism of carcinoma ⁃ associated fibroblasts on chemoresistance of epithelial ovarian cancer cells
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    目的:探讨癌相关成纤维细胞(carcinoma-associated fibroblasts,CAFs)对卵巢癌细胞化疗耐药性影响及机制。方法:通过CAFs和卵巢癌细胞Ovcar3共培养,采用流式细胞术检测顺铂(cis-diammin-odichloroplatinum,DDP)对共培养前后卵巢癌细胞凋亡率的改变;应用实时定量PCR、Western blot检测DDP对共培养前后卵巢癌细胞中PI3K、AKT、XIAP 的mRNA水平及其蛋白水平的变化;以及AKT 体外特异性阻断剂LY294002对CAFs引起化疗耐药的逆转作用。结果:CAFs与卵巢癌细胞共培养后,DDP诱导的卵巢癌细胞凋亡显著减少(P < 0.05);共培养组卵巢癌细胞中PI3K及XIAP 的mRNA表达水平明显高于对照组(P < 0.05);共培养后PI3K/XIAP蛋白表达显著升高(P < 0.05);磷酸化AKT(p-AKT)蛋白表达显著升高(P < 0.01)。抑制剂LY294002可显著降低XIAP蛋白表达。结论:CAFs可通过影响PI3K/AKT/XIAP信号通路,影响卵巢癌化疗耐药效应。

    Abstract:

    Objective:To investigate the effects of carcinoma-associated fibroblasts(CAFs)on chemoresistance of epithelial cancer cells and the underlying mechanism. Methods:Epithelial ovarian cancer cell Ovcar3 were exposed to cis-diammin-odichloroplatinum(DDP) with various concentrations and different duration,then CAFs cultured with Ovcar3 cell. The apoptosis of Ovcar3 cell was assessed by flow cytometry. The mRNA level of PI3K/AKT/XIAP was detected by real-time PCR. The protein level of PI3K,XIAP,AKT and AKT phosphorylation(p-AKT)was detected by Western blot. Signaling transduction inhibitors,LY294002 was used to block PI3K/AKT signaling pathways. Results:After co-culture,CAFs prevent DDP-induced apoptosis by upregulating the mRNA level and protein levels of PI3K/XIAP(P<0.05). In addition,p-AKT was enhanced by CAFs. Remarkably,inhibition of p-AKT by LY294002 can block the effects on DDP-induced XIAP up-regulation. Conclusion:These results demonstrate a novel mechanism by which CAFs regulates apoptosis and the possible involvement of the PI3K/AKT/XIAP survival pathway in chemoresistance of epithelial ovarian cancer cells.

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董丽华,孙 玮,傅士龙.癌相关成纤维细胞对上皮性卵巢癌细胞耐药性影响及机制初步研究[J].南京医科大学学报(自然科学版),2019,(2):191-195

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  • 收稿日期:2018-09-03
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  • 在线发布日期: 2019-03-06
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