ATPase Inhibitory Factor 1 Promotes Hepatocellular Carcinoma Progression After Insufficient Radiofrequency Ablation, and Attenuates Cell Sensitivity to Sorafenib Therapy

Jian Kong; Changyu Yao; Xuemei Ding; Shuying Dong; Shilun Wu; Wenbing Sun; Lemin Zheng

doi:10.3389/fonc.2020.01080

ATPase Inhibitory Factor 1 Promotes Hepatocellular Carcinoma Progression After Insufficient Radiofrequency Ablation, and Attenuates Cell Sensitivity to Sorafenib Therapy

Front Oncol. 2020 Jun 25:10:1080. doi: 10.3389/fonc.2020.01080. eCollection 2020.

Authors

Jian Kong¹, Changyu Yao¹, Xuemei Ding¹, Shuying Dong¹, Shilun Wu¹, Wenbing Sun¹, Lemin Zheng^{2

3}

Affiliations

¹ Department of Hepatobiliary Surgery, Beijing Chaoyang Hospital, Capital Medical University, Beijing, China.
² Key Laboratory of Molecular Cardiovascular Science of Ministry of Education, Key Laboratory of Cardiovascular Molecular Biology and Regulatory Peptides of Ministry of Health, Beijing Key Laboratory of Cardiovascular Receptors Research, School of Basic Medical Sciences, The Institute of Cardiovascular Sciences and Institute of Systems Biomedicine, Peking University Health Science Center, Beijing, China.
³ China National Clinical Research Center for Neurological Diseases, Tiantan Hospital, Advanced Innovation Center for Human Brain Protection, Capital Medical University, Beijing, China.

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.

Keywords: ATPase inhibitory factor 1; angiogenesis; epithelial-mesenchymal transition; hepatocellular carcinoma; radiofrequency ablation; sorafenib.