Insufficient radiofrequency ablation promotes epithelial-mesenchymal transition of hepatocellular carcinoma cells through Akt and ERK signaling pathways.
Insufficient radiofrequency ablation promotes epithelial-mesenchymal transition of hepatocellular carcinoma cells through Akt and ERK signaling pathways.
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射频消融不足通过 Akt 和 ERK 信号通路促进肝细胞癌细胞上皮间质转化。
DOI：
10.1186/1479-5876-11-273
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发表时间：
2013-10-29
影响因子：
7.4
通讯作者：
Zheng L
中科院分区：
文献类型：
--
作者：
Dong S;Kong J;Kong F;Kong J;Gao J;Ke S;Wang S;Ding X;Sun W;Zheng L
最近报告了射频消融（RFA）不充分后的残留肿瘤进展。然而，上皮间质转化（EMT），这是一个关键的过程，驱动癌症转移，是否参与了肿瘤的进展不足RFA后还没有得到很好的理解。使用人肝细胞癌（HCC）细胞系SMMC 7721和Huh 7。使用水浴（47°C，5分钟、10分钟、15分钟、20分钟和25分钟逐渐）模拟RFA不足。MTT法检测肝癌细胞的体外增殖情况。transwell法检测肝癌细胞的迁移和侵袭能力。Western blot检测RFA不足后肝癌细胞分子水平的变化。用LY 294002和PD 98059处理HCC细胞。采用裸鼠异位移植瘤模型和尾静脉转移试验评价SMMC 7721细胞在射频消融不足后的体内生长和转移潜力。在体外，SMMC 7721和Huh 7细胞（分别命名为SMMC 7721-H和Huh 7-H）在射频消融不足后的增殖、迁移和侵袭能力分别增加6.4%和23.6%、33.2%和66.1%、44.1%和57.4%。在SMMC 7721-H和Huh 7-H细胞中观察到EMT的分子变化。LY 294002和PD 98059可抑制SMMC 7721-H和Huh 7-H细胞的EMT。SMMC 7721-H细胞在体内也表现出比SMMC 7721细胞更大的肿瘤尺寸（1440.8 ± 250.3 mm 3对1048.56 ± 227.6 mm 3）和更多的肺转移（增加97.4%）。PCNA、N-cadherin、MMP-2、MMP-9在SMMC 7721-H肿瘤中的表达也较高。RFA不足可直接促进肝癌细胞的侵袭和转移。RFA不足可能通过Akt和ERK信号通路促进HCC细胞的EMT。
Residual tumor progression after insufficient radiofrequency ablation (RFA) has been recently reported. However, whether epithelial-mesenchymal transition (EMT), which is a key process that drives cancer metastasis, is involved in the tumor progression after insufficient RFA is not well understood. Human hepatocellular carcinoma (HCC) cell lines SMMC7721 and Huh7 were used. Insufficient RFA was simulated using a water bath (47°C 5 min, 10 min, 15 min, 20 min and 25 min gradually). MTT assay was used to evaluate the proliferation of HCC cells in vitro. Migration and invasion of HCC cells were determined by transwell assay. The molecular changes in HCC cells after insufficient RFA were evaluated by western blot. LY294002 and PD98059 were used to treat HCC cells. An ectopic nude mice model and a tail vein metastatic assay were used to evaluate the growth and metastatic potential of SMMC7721 cells in vivo after insufficient RFA. SMMC7721 and Huh7 cells after insufficient RFA (named as SMMC7721-H and Huh7-H respectively) exhibited enhanced proliferation, migration and invasion (6.4% and 23.6%, 33.2% and 66.1%, and 44.1% and 57.4% increase respectively) in vitro. Molecular changes of EMT were observed in SMMC7721-H and Huh7-H cells. LY294002 and PD98059 inhibited the EMT of SMMC7721-H and Huh7-H cells. SMMC7721-H cells also exhibited larger tumor size (1440.8 ± 250.3 mm3 versus 1048.56 ± 227.6 mm3) and more lung metastasis (97.4% increase) than SMMC7721 cells in vivo. Higher expression of PCNA, N-cadherin and MMP-2 and MMP-9, was also observed in SMMC7721-H tumors. Insufficient RFA could directly promote the invasiveness and metastasis of HCC cells. Insufficient RFA may promote the EMT of HCC cells through Akt and ERK signaling pathways.
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