Metformin exhibits the anti-proliferation and anti-invasion effects in hepatocellular carcinoma cells after insufficient radiofrequency ablation.
Metformin exhibits the anti-proliferation and anti-invasion effects in hepatocellular carcinoma cells after insufficient radiofrequency ablation.
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二甲双胍对射频消融不充分后的肝癌细胞具有抗增殖和抗侵袭作用
DOI：
10.1186/s12935-017-0418-6
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发表时间：
2017
影响因子：
5.8
通讯作者：
Sun W
中科院分区：
文献类型：
--
作者：
Zhang Q;Kong J;Dong S;Xu W;Sun W
背景：射频消融（RFA）不充分后肝细胞癌（HCC）进展的机制和预防已经初步研究，因此，需要研究新的策略来预防这一过程。二甲双胍是否能够抑制RFA不足后HCC的生长，并进一步预防残余HCC的进展，目前尚不清楚。方法采用smtt法、菌落形成法和transwell法观察细胞活力、迁移和侵袭情况。采用Western blot和免疫组织化学方法观察蛋白表达情况。采用异种移植模型评价肝癌细胞在体内的生长情况。结果二甲双胍抑制RFA不足后HepG2和SMMC7721细胞（命名为HepG2- h和SMMC7721- h）增殖、迁移和侵袭的增强。二甲双胍通过AMPK/PTEN通路解除RFA不足后HepG2和SMMC7721细胞中p-Akt的表达。HepG2-H细胞在体内也表现出更大的肿瘤大小。HepG2-H肿瘤中Ki-67、CD31表达升高，E-cadherin表达降低。二甲双胍阻断体内RFA不足后HepG2细胞的增强生长。二甲双胍对裸鼠无明显毒性。结论甲氧美明对RFA不充分后肝癌细胞的生长有抑制作用，可用于预防RFA后肝癌的进展。
BackgroundThe mechanisms and prevention of progression of hepatocellular carcinoma (HCC) after insufficient radiofrequency ablation (RFA) has been preliminarily investigated, therefore, new strategy needs to be investigated to prevent the process. Whether metformin could be used to inhibit the growth of HCC after insufficient RFA and further prevent the progression of residual HCC remains unclearly.MethodsMTT assay, colony formation assay and transwell assay were used to observe the cell viability, migration and invasion. Western blot and immunohistochemistry methods were used to observe the expression of proteins. Xenograft model was used to evaluate the growth of HCC cells in vivo.ResultsMetformin inhibited the enhanced proliferation, migration and invasion of HepG2 and SMMC7721 cells after insufficient RFA (named as HepG2-H and SMMC7721-H). Metformin deregulated the expression of p-Akt in HepG2 and SMMC7721 cells after insufficient RFA through AMPK/PTEN pathway. HepG2-H cells also exhibited larger tumor size in vivo. Higher expression of Ki-67 and CD31 and lower expression of E-cadherin were observed in HepG2-H tumors. Metformin blocked the enhanced growth of HepG2 cells in vivo after insufficient RFA. Metformin had no apparent toxicity on nude mice.ConclusionsMetfromin inhibited the growth of HCC cells after insufficient RFA, and may be used to prevent the progression of HCC after RFA.