Abstract
Epithelial-mesenchymal transition (EMT) and angiogenesis is involved in tumor progression after radiofrequency ablation (RFA). ATPase inhibitory factor 1 (IF1) is a bad predictor of prognosis. Sorafenib inhibited EMT of hepatocellular carcinoma (HCC) after RFA. Whether IF1 promotes the EMT and angiogenesis of HCC and attenuates the effect of sorafenib after insufficient RFA is investigated. In this study, higher expression of IF1 was found in residual tumor after insufficient RFA. Hep3B or Huh7 cells after insufficient RFA were designated as Hep3B-H or Huh7-H cells in vitro. Hep3B-H or Huh7-H cells exhibited enhanced capacities of colony formation, migration, and increased expression of EMT associated markers and IF1 compared with Hep3B or Huh7 cells. IF1 knockdown in Hep3B-H or Huh7-H cells decreased the colony formation and migratory capacity, and IF1 overexpression in Hep3B or Huh7 cells increased these capacities. IF1 in HCC cells directly and indirectly affected angiogenesis of TAECs after insufficient RFA. IF1 promoted HCC cells growth and metastasis after insufficient RFA. IF1 increased HCC cells resistance after insufficient RFA to sorafenib. Higher IF1 expression indicated poor disease survival in HCC patients after sorafenib therapy. NF-κB activation induced by IF1 attenuated the effect of sorafenib on HCC cells after insufficient RFA. Our results demonstrated that IF1 promotes the EMT and angiogenesis, and attenuates HCC cell sensitivity to sorafenib after insufficient RFA through NF-κB signal pathway.
Highlights
Hepatocellular carcinoma (HCC) is the sixth most common neoplasm and the third leading cause of cancer death [1]
Tumor progression happens when insufficient radiofrequency ablation (RFA) is performed, and Epithelial-mesenchymal transition (EMT) and angiogenesis may be involved in the process
Consistent with before finding, we found that inhibitory factor 1 (IF1) promoted the EMT and angiogenesis of hepatocellular carcinoma (HCC) cells and attenuated sensitivity of sorafenib to inhibit growth and metastasis in HCC through NF-κB signal pathways
Summary
Hepatocellular carcinoma (HCC) is the sixth most common neoplasm and the third leading cause of cancer death [1]. Previous studies have elaborated the mechanism involving in tumor progression in HCC after RFA. LncRNA FUNDC2P4 down-regulation promoted EMT through decreasing E-cadherin expression in residual HCC after insufficient RFA [13]. Tumor associated endothelial cells (TAECs) showed enhanced angiogenesis and facilitated invasiveness of residual HCC after insufficient RFA [16]. We assumed that IF1 played the role in the EMT and angiogenesis of HCC and was involved in the effect of sorafenib after insufficient RFA. We showed that IF1 participated in the EMT and angiogenesis of HCC after insufficient RFA. Ectopic overexpression of IF1 attenuated the suppressing effect of sorafenib on EMT and angiogenesis in HCC after RFA, and higher expression of IF1 in HCC tissue indicated low disease free survival for HCC patients receiving resection and sorafenib. Our results provide an explanation for progression of HCC after insufficient RFA
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