Studies on the mechanism of inhibition of Tumor Growth Factor-β1(TGF-β1)-induced apoptosis in human hepatoma cell line Hep3B by insulin and TPA

• Main Authors: Chen-Chi Liao, 廖珍琦
• Other Authors: Chen-Kung Chou
• Format: Others
• Language: zh-TW
• Published: 1999
• Online Access: http://ndltd.ncl.edu.tw/handle/96597730544325709677

碩士 === 國立陽明大學 === 遺傳學研究所 === 87 === Abstract The transforming growth factor β 1 (TGF-β1) plays a critical role in controlling the balance between cell growth and cell death. This tightly regulated homeostasis between cell growth and apoptosis can be broken during hepatocarcinognesis and in carious liver diseases. When TGF-β1 along is added to human hepatoma cell line, Hep3B, apoptosis is induced. This effect, however, can be prevented when insulin or TPA is added with TGF-β1 into cultured Hep3B. In current study, we are interested in whether insulin and TPA function through the same signal transduction pathway to antagonize TGF-β1 induced apoptosis. Through an activity inhibitor, wortamannin, PI3K has been shown to be involved in insulin's anti-apoptotic effect induced by TGF-β1. We used another specific PI3K activity inhibitor, LY294002, and confirmed the authenticity of the result mentioned. Furthermore, through PI3K and PKC family specific activity inhibitors, we found that insulin prevents TGF-β1 induced apoptosis via PI3K, not PKC. TPA, on the other hand, utilizes PKC, not PI3K to inhibit TGF-β1induced apoptosis. During our study, we also found synergistic effect between low concentration of insulin (10-9M) and TPA (10 ng/ml). This observed synergistic effect between low dosage of insulin and TPA is abolished in the presence of PI3K and PKC family inhibitors. Last but not the least, our result also suggests the possibility of Mcl-1 and JNK's involvement in the anti-apoptotic activity of TPA on human hepatoma cells.