Abstract 17: Hepatitis C virus (HCV) core protein potentiates proangiogenic activity of hepatocellular carcinoma (HCC) cells

Abstract

Abstract Background: Recent clinical trials found that sorafenib may have better efficacy for HCV-related HCC than HCC with other etiologies. HCV core protein has been found to influence the mitogen-activated protein kinase pathway, which is one of the targets of sorafenib. We thus planned this study to examine the effect of HCV core protein overexpression on HCC cells. Methods: We stably expressed HCV core protein in Huh7, a HCC cell line, using a lentivirus based vector S2. Two stable clones were selected for experiments. One clone (Huh7-core-high) expressed a higher amount of HCV core protein than the other (Huh7-core-low). Huh7 expressing the empty vector (Huh7-S2) served as a control. We compared the cytotoxicity of sorafenib in these cells using the MTT assay. Tube formation analysis and Matrigel plug assay were performed to evaluate the angiogenic activity. Results: Huh7-core-high and Huh7-core-low cells did not show increased cell proliferation compared to Huh7-S2 cells. Sorafenib showed similar in vitro cytotoxicity for Huh7-core-high, Huh7-core-low, and Huh7-S2 cells. Overexpression of HCV core protein potentiates proangiogenic activity of Huh7 cells dose-dependently. In tube formation analysis, Huh7-core-high induced more potent angiogenesis than Huh7-S2 cells with more total tube lengths (p = 0.02), mean tube lengths (p = 0.04), mean tube areas (p = 0.04), branch points (p = 0.03), and nodes (p < 0.01). Huh7-core-low cells induced stronger angiogenesis than Huh7-S2 cells with more total tube lengths (p = 0.05) and branch points (p = 0.01). By Matrigel plug assay, Huh7-core-high and Huh7-core-low cells dose-dependently induced stronger angiogenesis in mice compared to Huh7-S2 cells with significantly higher hemoglobin levels in the Matrigel plugs. Conclusions: HCV core protein expression potentiates the proangiogenic activity of HCC, both in vitro and in vivo. (This work was supported by grants NSC98-3112-B-002-038, NSC101-2314-B-002-141, 100CAP1020-2 & 102-2314-B-002-120.) Citation Format: Yu-Yun Shao, Chung-Yi Huang, Jun-Wei Chen, Chih-Hung Hsu, Ann-Lii Cheng. Hepatitis C virus (HCV) core protein potentiates proangiogenic activity of hepatocellular carcinoma (HCC) cells. [abstract]. In: Proceedings of the 105th Annual Meeting of the American Association for Cancer Research; 2014 Apr 5-9; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2014;74(19 Suppl):Abstract nr 17. doi:10.1158/1538-7445.AM2014-17