缺氧诱导前列腺基质细胞HIF-1α与自噬在前列腺癌中的作用与机制研究  

The role and mechanism of hypoxia-induced prostate stromal cell HIF-1α and autophagy in prostatecance

作　　者：黄光毅 白俊超 蒋则平 朱武安 Huang Guangyi

机构地区：[1]浙江大学医学院附属第四医院,322000

出　　处：《浙江临床医学》2022年第7期965-969,共5页Zhejiang Clinical Medical Journal

摘　　要：目的探讨低氧诱导因子-1(HIF-1α)在缺氧诱导的前列腺基质细胞自噬调节与增殖分化发生的机制.方法通过不同氧气浓度和不同缺氧时间筛选前列腺基质细胞WPWY-1细胞增殖最佳低氧培养条件,并通过自噬抑制剂、自噬促进剂、Ad-HIF-1α表达载体、Ad-siHIF-1α表达载体分别处理WPWY-1细胞,在低氧环境培养后检测各组细胞增殖活力、自噬率,及HIF-1α,LC3Ⅱ,Beclin 1,转化生长因子-β1(TGF-β1),成纤维细胞生长因子-2(FGF-2)和FGF-7的表达.结果低氧能促进前列腺基质永生化细胞WPWY-1增殖,以氧浓度为10%,培养时间为24 h最佳.在低氧培养条件下,自噬抑制剂或Ad-siHIF-1α表达载体处理后WPWY-1细胞增殖活力,LC3Ⅱ,Beclin1,TGF-β1,FGF-2和FGF-7的表达降低(P<0.05),细胞自噬率增加(P<0.05);自噬促进剂或Ad-HIF-1α表达载体处理后WPWY-1细胞增殖活力,LC3Ⅱ,Beclin1,TGF-β1,FGF-2和FGF-7的表达增加(P<0.05),细胞自噬率降低(P<0.05).结论低氧诱导前列腺基质细胞HIF-1α表达上调,通过增强自噬通路中的信号蛋白Beclin1和LC3II的表达,调控细胞自噬水平,从而促进细胞释放TGF-β1、FGF-2、FGF-7等细胞生长因子.Objective To investigate the mechanism of hypoxia inducible factor-1α(HIF-1α)in the regulation of autophagy and proliferation differentiation of prostate stromal cells induced by hypoxia.Methods Select the best hypoxia culture conditions for proliferation of prostate stromal cell WPWY-1 by different oxygen concentration and hypoxia time,and treat wpwy-1 cells with autophagy inhibitor,autophagy promoter,ad-HIF-1αexpression vector and ad-siHIF-1αexpression vector respectively.After incubation in low oxygen environment,the proliferation activity,autophagy rate and the expression of HIF-1α,LC3 II,Beclin1,TGF-β1,FGF-2 and FGF-7 were detected.Results Hypoxia can promote the proliferation of prostate stromal immortalized cell WPWY-1,the best concentration of oxygen was 10%,and the best culture time was 24 hours.Under the condition of hypoxia,the proliferation of WPWY-1 cells treated with autophagy inhibitor or ad-siHIF-1αexpression vector decreased significantly in LC3II,Beclin1,TGF-β1,FGF-2 and FGF-7 expression(P<0.05),increased significantly in autophagy rate(P<0.05).And the proliferation of WPWY-1 cells treated with autophagy promoter or ad-HIF-1αexpression vector increased significantly in LC3II,Beclin1,TGF-β1,FGF-2 and FGF-7 expression(P<0.05),decreased significantly in autophagy rate(P<0.05).Conclusion Up-regulation of HIF-1αexpression with Hypoxia in prostate stromal cells,regulates the level of autophagy by enhancing the expression of Beclin1 and LC3II,thus promotes the release of TGF-β1,FGF-2,FGF-7 and other cell growth factors.

关 键 词：低氧诱导因子 低氧 自噬 WPWY-1 前列腺癌 

分 类 号：R737.25[医药卫生—肿瘤]