文章摘要
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,2019,(2):191~195
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
Effects and mechanism of carcinoma ⁃ associated fibroblasts on chemoresistance of epithelial ovarian cancer cells
投稿时间:2018-09-03  
DOI:10.7655/NYDXBNS20190206
中文关键词: 癌相关成纤维细胞  卵巢癌  共培养  化疗耐药
英文关键词: carcinoma⁃associated fibroblasts  epithelial ovarian carcinoma  cell coculture  chemoresistance
基金项目:江苏省妇幼保健科研项目(F201438)
作者单位
董丽华 南京医科大学第一附属医院妇科江苏 南京 210029 
孙 玮 南京医科大学第一附属医院妇科江苏 南京 210029 
傅士龙 南京医科大学第一附属医院妇科江苏 南京 210029 
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中文摘要:
      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。
英文摘要:
      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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