Sorafenib suppresses the epithelial-mesenchymal transition of hepatocellular carcinoma cells after insufficient radiofrequency ablation

Abstract

BackgroundEpithelial-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.MethodsInsufficient 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.ResultsHepG2 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.ConclusionsSorafenib inhibited the EMT of HCC cells after insufficient RFA, and may be used to prevent the progression of HCC after RFA.Electronic supplementary materialThe online version of this article (doi:10.1186/s12885-015-1949-7) contains supplementary material, which is available to authorized users.

Targeting autophagy enhances heat stress-induced apoptosis via the ATP-AMPK-mTOR axis for hepatocellular carcinoma

“…Arrows represent promotion events; blunt arrows indicate suppression events. treatment in vivo, a xenograft tumor model was established according to previous studies [5,38,39]. The results revealed that heat treatment activated autophagy and autophagic flux in xenograft tumor tissues.…”

Effect of a hypoxic microenvironment after radiofrequency ablation on residual hepatocellular cell migration and invasion

“…Sorafenib has been approved as the first‐line systemic drug for advanced HCC. Previous studies indicated that sorafenib suppresses the transition of residual HCC cells from epithelial phenotype to the mesenchymal phenotype after insufficient RFA . Another study suggested that RFA combined with sorafenib exerts a better curative effect in terms of tumor suppression than RFA alone, probably through inhibiting HIF‐1α and vascular endothelial growth factor expression .…”

“…Previous studies indicated that sorafenib suppresses the transition of residual HCC cells from epithelial phenotype to the mesenchymal phenotype after insufficient RFA. (28) Another study suggested that RFA combined with sorafenib exerts a better curative effect in terms of tumor suppression than RFA alone, probably through inhibiting HIF-1a and vascular endothelial growth factor expression. (29) However, Zhao D et al revealed that sorafenib upregulates HIF-2a by switching the hypoxia response from HIF-1a to HIF-2a-dependent pathways, resulting in the activation of the TGF-a/EGFR pathway, and subsequently the phosphorylation of STAT3, AKT and ERK, which contributes to the resistance of HCC cells to sorafenib.…”

MEIS-1 level in unresectable hepatocellular carcinoma can predict the post-treatment outcomes of radiofrequency ablation

“…Epithelial-mesenchymal transition, of the tumor cells often changes [ 36 ]. Previous research suggested that incomplete ablation in RFA may induce cellular stress and lead to pathological changes [ 37 , 38 ]. Zhu et al suggested that overexpression of MEIS-1 inhibits the EMT process and decreases the expression of pro-survival genes in clear cell renal cell carcinomas [ 25 ].…”