摘要: |
目的 探讨肝癌细胞系 HepG2 细胞缺氧状态下过氧化物酶体增殖物激活受体 γ 辅激活因子 -1α(PGC-1α)、趋 化因子受体 4(CXCR4)及 E- 钙黏蛋白的表达情况,及其在肝癌侵袭转移中的作用。 方法 将 PGC-1α 小干扰 RNA(siPGC-1α) 转染 HepG2 细胞,应用 RT-PCR 及 Western blot 法检测 PGC-1α、CXCR4 及 E- 钙黏蛋白的 mRNA 及蛋白表达水平,Transwell 试 验分析 HepG2 细胞迁移情况。 结果 与常氧状态下比较,缺氧状态下 HepG2 细胞的 PGC-1α、CXCR4 表达水平均增高(均 P<0.05),E- 钙黏蛋白表达水平降低(P<0.05),且迁移细胞数目增多。在 HepG2 细胞转染 siPGC-1α 后,CXCR4 及 E- 钙黏蛋白表达 水平均逆转,同时迁移细胞数目减少(均 P<0.05),而加入 CXCR4 拮抗剂(AMD3100)后,E- 钙黏蛋白表达水平增高,迁移细胞数目 减少(均 P<0.05)。 结论 缺氧 /PGC-1α/CXCR4 信号通路在调控 E- 钙黏蛋白表达以及肝癌细胞迁移中起着重要作用,是肝癌侵 袭转移的新治疗靶点。 |
关键词: 过氧化物酶体增殖物激活受体 γ 辅激活因子 -1α 趋化因子受体 4 HepG2 细胞 E- 钙黏蛋白 |
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Roles of hypoxic /PGC-1α/CXCR4 signaling pathway in migration of hepatocellular carcinoma |
SHEN Weimin, LU Bei, LIU Ling
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Hangzhou First People's Hospital
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Abstract: |
Objective To investigate the roles of hypoxic/CXCR4/PGC-1α pathway in migration of human hepatocellular carcinoma cells line HepG2. Methods HepG2 cells were transfected with siPGC-1α and then the expression of PGC-1α, CXCR4 and E-cadherin mRNA and protein was detected by RT-PCR and Western blotting, respectively. Cell migration was assessed by Transwell method. Results Exposure of HepG2 cells to hypoxia resulted in the overexpression of PGC-1α, CXCR4 (both P<0.05) , down-regulated expression of E-cadherin (P<0.05) and increased cell migration compared to normoxic condition(P<0.05) . After HepG2 cells were transfected with siPGC-1α the overexpression of CXCR4, reduced expression of E-cadherin and increased cell migration were reversed, and the same results were obtained when HepG2 cells were treated with CXCR4 antagonist AMD3100(P <0.05). Conclusion The hypoxic/PGC-1α/CXCR4 pathway may play a significant role in regulating the expression of E-cadherin and migration of HepG2 cells, which might be a novel therapeutic target for invasion and metastasis of hepatocellular carcinoma. |
Key words: PGC-1伪 CXCR4 HepG2 cells E-cadherin |