Effect of TALEN-mediated IL-6 knockout on cell proliferation, apoptosis, invasion and anti-cancer therapy in hepatocellular carcinoma (HCC-LM3) cells

作者：Peng–Yuan Zhuang, Kewei Zhang, Jiandong Wang, Xueping Zhou, Yingbin Liu, Zhi-Wei Quan, Jun Shen · 发表于：Oncotarget · 年份：2017 · DOI：10.18632/oncotarget.20946 · 被引用次数：18 · 研究领域：Cancer, Hypoxia, and Metabolism、Hepatocellular Carcinoma Treatment and Prognosis、Immune cells in cancer

// Peng-Yuan Zhuang 1, * , Ke-Wei Zhang 1, * , Jian-Dong Wang 1 , Xue-Ping Zhou 1 , Ying-Bin Liu 1 , Zhi-Wei Quan 1 and Jun Shen 1 1 Department of General Surgery, Xinhua Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, People’s Republic of China * These authors have contributed equally to this work Correspondence to: Jun Shen, email: shenjun@xinhuamed.com.cn Keywords: hepatocellular carcinoma, IL-6, TALEN Received: June 05, 2017     Accepted: July 26, 2017     Published: September 15, 2017 ABSTRACT Purpose: To determine the exact effect of Interleukin-6 (IL-6) on tumor cell proliferation, apoptosis, invasion, and anti-cancer therapy in hepatocellular carcinoma (HCC). Experimental Design: IL-6 was disrupted by transcription activator-like effector nucleases (TALEN) in HCCLM3 cells, and was used to evaluate the role of IL-6 on tumor cell proliferation, apoptosis, invasion and key signaling pathways involved in sorafenib and/or IFNα therapy. Results: IL-6 has no direct effect on cell proliferation and invasion but promotes cell apoptosis and up-regulate IL-33 and VEGF-A expression. IL-6 could attenuate the anti-proliferation effect by sorafenib and combination therapy but facilitate the pro-apoptosis of the combination therapy and augment the pro-invasive effect induced by single treatment. IL-6 could down-regulate p-STAT3, however up-regulate the p-MEK/p-ERK and NF-kB/iNOS expression, and it also facilit...