The role of TLR4 activation in hepatocellular carcinoma

• Main Authors: Cheng, Yi-Chen, 程怡蓁
• Other Authors: Tseng, Ping-Hui
• Format: Others
• Language: zh-TW
• Published: 2013
• Online Access: http://ndltd.ncl.edu.tw/handle/64472792013094662362

碩士 === 國立陽明大學 === 生化暨分子生物研究所 === 101 === Inflammation plays the important role in hepatocellular carcinoma（HCC）development. The toll-like receptors（TLRs） are involved in innate immunity and cause inflammation response. In previous studies, TLRs are also expressed in liver cells, which are associated to liver disease, such as alcoholic hepatitis, and liver fibrosis. In diethylnitrosamine（DEN）induced animal model, it was not clear how TLR4 participated in hepatocellular carcinoma. Therefore, we wanted to know the role of TLR4 in hepatocellular carcinoma by human hepatoma cell line Huh7 and mouse hepatoma cell C2, both express relatively high amount of TLR4. The result indicated that activation of TLR4 promoted growth of hepatocellular carcinoma cells by using MTT assay, trypan blue dye exclusion assay and colony formation assay. The human hepatoma cell line PLC5 which has relatively low expression of TLR4 cultured with LPS（10 ng/mL） in order to simulated chronic inflammation. The data showed that chronic inflammation changed the expression of TLRs, and it was possibly regulated through the activation of inflammation-related microRNA pathway. Previous studies indicated that the tumor microenvironment could affect tumor development, so it was important to know whether the activation of TLR4 by endogenous molecules could influence the growth of hepatocellular carcinoma cells. The data showed that Huh7-conditioned medium could promote the cell growth, and we found that the fraction of Huh7-conditioned medium in 10 ~ 30KD promoted cell growth. Mass spectrometry analysis was used to identify endogenous molecules. To sum up, the activation of TLR4 in hepatocellular carcinoma affected HCC cells growth, and there were endogenous molecules which affected HCC cells growth through the activation of TLR4.