Sorafenib suppresses the epithelial-mesenchymal transition of hepatocellular carcinoma cells after insufficient radiofrequency ablation.
Sorafenib suppresses the epithelial-mesenchymal transition of hepatocellular carcinoma cells after insufficient radiofrequency ablation.
复制标题
射频消融不充分后，索拉非尼抑制肝细胞癌细胞的上皮间质转化。
DOI：
10.1186/s12885-015-1949-7
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发表时间：
2015-11-30
期刊：
影响因子：
3.8
通讯作者：
Sun W
中科院分区：
文献类型：
--
作者：
Dong S;Kong J;Kong F;Kong J;Gao J;Ji L;Pan B;Chen L;Zheng L;Sun W
上皮间质转化(EMT)在不足射频消融(RFA)后肝细胞癌(HCC)的发生发展中起重要作用。然而，索拉非尼能否在RFA不足后抑制肝细胞癌的EMT，进一步阻止残留肝细胞癌的进展仍是个未知数。用水浴(47℃5、10、15、20和25分钟逐渐)模拟RFA不足。采用四甲基偶氮唑盐比色法和Transwell法观察索拉非尼对体外培养的人肝癌细胞株HepG2和SMMC7721在RFA不足后的存活、迁移和侵袭能力的影响。在RFA不足后，用Western印迹和ELISAs分析索拉芬处理后肝癌细胞的分子变化。采用异位裸鼠模型，观察索拉非尼对射频消融不足的人肝癌细胞株HepG2体内生长的影响。RFA不足后的HepG2和SMMC7721细胞(命名为HepG2-H和SMMC7721-H)在体外表现出更强的存活率、迁移和侵袭能力。索拉非尼可抑制RFA不足后增强的HepG2和SMMC7721细胞的活力、迁移和侵袭能力。在HepG2-H和SMMC7721-H细胞中观察到EMT的分子变化。索拉非尼对HepG2-H和SMMC7721-H细胞的EMT均有抑制作用。在体内，HepG2-H细胞也表现出较大的肿瘤体积。在HepG2-H肿瘤中，增殖细胞核抗原、Ki67、N-钙粘蛋白、基质金属蛋白酶-2和基质金属蛋白酶-9也有较高的表达。索拉非尼阻断RFA不足后体内增强的HepG2细胞生长。索拉非尼可抑制RFA不足后肝癌细胞的EMT，可能用于阻止RFA后肝癌的进展。本文的在线版本(doi：10.1186/s12885-0151949-7)包含补充材料，授权用户可以使用。
Epithelial-mesenchymal transition (EMT) played an important role in the progression of hepatocellular carcinoma (HCC) after insufficient radiofrequency ablation (RFA). However, whether sorafenib could be used to suppress the EMT of HCC after insufficient RFA and further prevent the progression of residual HCC remains poorly unknown. Insufficient RFA was simulated using a water bath (47 °C 5, 10, 15, 20 and 25 min gradually). MTT assay and transwell assay were used to evaluate the effects of sorafenib on viability, migration and invasion of HepG2 and SMMC7721 cells after insufficient RFA in vitro. After insufficient RFA, the molecular changes in HCC cells with the treatment of sorafeinb were evaluated using western blot and ELISAs. An ectopic nude mice model was used to evaluate the effect of sorafenib on the growth of HepG2 cells in vivo after insufficient RFA. HepG2 and SMMC7721 cells after insufficient RFA (named as HepG2-H and SMMC7721-H) exhibited enhanced viability, migration and invasion in vitro. Sorafenib inhibited the enhanced viability, migration and invasion of HepG2 and SMMC7721 cells after insufficient RFA. Molecular changes of EMT were observed in HepG2-H and SMMC7721-H cells. Sorafenib inhibited the EMT of HepG2-H and SMMC7721-H cells. HepG2-H cells also exhibited larger tumor size in vivo. Higher expression of PCNA, Ki67, N-cadherin, MMP-2 and MMP-9, was also observed in HepG2-H tumors. Sorafenib blocked the enhanced growth of HepG2 cells in vivo after insufficient RFA. Sorafenib inhibited the EMT of HCC cells after insufficient RFA, and may be used to prevent the progression of HCC after RFA. The online version of this article (doi:10.1186/s12885-015-1949-7) contains supplementary material, which is available to authorized users.