Resveratrol enhance Sorafenib drug sensitivity in HCC cell line through inhibiting nuclear factor-kappa B

• Main Authors: Chia Hui Chen, 陳嘉惠
• Other Authors: S. W. Wang
• Format: Others
• Published: 2013
• Online Access: http://ndltd.ncl.edu.tw/handle/64787720322178470892

碩士 === 長庚大學 === 生物醫學研究所 === 101 === Hepatocellular carcinoma (HCC) is the second leading cancer related death in Taiwan. The incidence of HCC is high because the prevalence of Hepatitis B Virus infection which is related to chronic hepattis, cirrhosis and tumor formation. The chronic liver inflammation may turn on the nuclear factor kappa B(NF-kB) pathway to promote hepatocyte proliferation lead to hepatocarcinogenesis. Furthermore, in the inflammatory micreoenviroment of the liver, elevation of inflammatory cytokine, such as tumor necrosis factor-alpha(TNF-α), may activate some oncogenic signal transduction to promote HCC cancer cell proliferation and anti-apoptosis. Resveratrol is a type of natural phenol, which was found in the peer of red grapes and other fruits. Studies have showed that Resveratrol served as anti-inflammatory and anti-cancer effect. In this study, we examined NF-B pathway in both HCC tissue and HCC cell lines. NF-kB signaling was more overexpressed and activated on tissues from HCC portal vein thrombosis in compare to tissues with none, which suggested that advanced HCC frequently presented NF-kB activation. Resveratrol could effectively inhibit TNF-α mediated NF-kB activation on HCC cells. Which resulted in inhibition of cell proliferation and enhancement of cell apoptosis. Sorafenib, a target therapy approved by FDA for advanced HCC, did not block TNF-αmediated NF-kB activation on HCC cells. However, inhibition of NF-kB activity enhancrd the sensitivity of sorafenib on both Hep3B and PLC/PRF/5 cells. Similarly, the cytotoxicity of Sorafenib was also enhanced in combination with Resveratrol. According to these observations indicated that inhibition NF-kB pathway by Resveratrol might become other anti-cancer strategy for HCC, especially in combination with Sorafenib for treament of advanced-stage HCC.