| Summary: | 碩士 === 慈濟大學 === 生命科學研究所 === 96 === Liver cancer, also called hepatoma, is one of the most common and devastating human malignant tumors in the world. The highest incidence rates of liver cancer are in Asian areas such as Taiwan and China. In these areas, hepatoma is highly associated with the infection of Hepatitis B virus (HBV), a hepadnaviruses. During infection, HBV related proteins have some effects on regulating the development of malignancies and response of tumor cells to various treatments. Because of unapparent pathology and metastasis mechanism, none of the advanced therapy has significantly improved the extremely poor prognosis of patients with hepatoma. The development of new therapeutic and preventive strategies targeted at apoptosis induction could be an important goal to control hepatoma. For decreasing the side effect produced by the artificial chemicals, the purpose of our study is to find the pure compound of plant extract which produce less side effect. Ursolic acid (UA) and its derivative, oleanolic acid (OA), are two glycyrrhetinic acid related pentacyclic triterpenoids that had been reported to have the anti-proliferative effect on several tumor cells. To investigate the anti-tumor effect of UA and OA on hepatoma, Hep G2 and HBV-containing Hep G2.2.15 cells were treated with these compounds. In our result, we observed the apoptotic evidence of DNA fragmentation, coincided with the protein expression of ICAD and g-H2AX. Flow cytometric analysis showed that both UA and OA induced apoptosis in Hep G2 cells through mitochondrial pathway but in HBV-containing Hep G2.2.15 cells only UA treatment resulted in the same effects. The effect of UA was more significant than that of OA in both cell lines. Besides, the activation of caspases indicated that the mitochondria-mediated pathway and its upstream the bcl-2 family and caspase-8 activation were involved in the UA and OA-induced anti-proliferation and apoptosis in both cell lines. Our results also demonstrate that UA and OA differentially induce apoptosis in Hep G2 and HBV-containing Hep G2.2.15 cells through the mitochondrial/caspase-dependent pathway.
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