| Summary: | 碩士 === 國立陽明大學 === 藥理學研究所 === 88 === Liver cancer is a worldwide disease. In Taiwan, liver cancer is the leading cause of cancer death. Epidemiology studies showed that males have higher incidence of hepatocellular carcinoma (HCC) than females. Clinical studies further showed that sex is one of the risk factors in HCC. Recently, many studies reported that 2-methoxyestradiol (2-ME) could inhibit angiogenesis and tumor cell growth. 2-ME is one of estrogen metabolites. Whether 2-ME can inhibit HCC growth is not clear.
Results from this study show that 2-ME induced morphological changes in ML-1 cells at 5~ 100 uM. In addition, 2-ME reduced cell viability and inhibited cell growth in a dose and time dependent manner. The viability of ML-1 cells treated with 2-ME (5-100 uM) for 24 hours decreased from 84% to 67%. At 72 hours after 2-ME (5-100 uM) treatment, the viability of ML-1 cells decreased from 48% to 31%. Using flowcytometric analysis, it was found that treatment of ML-1 cell with 2-ME resulted in G2-M cycle arrest prior to cell death. Apoptosis peak was observed in ML-1 cells treated with 2-ME (2.5 uM) for 24- 48 hours. 2-ME treatment of ML-1 cells resulted in increased level of reactive oxygen species (ROS) dose dependently. Treatment of BALB/c mice bearing ML-1 tumors with 2-ME (1.875 mg / 0.1 ml DMSO + olive oil) inhibited tumor growth in vivo. The tumor volume of the 2-ME group was 50% smaller than the control group.
In conclusion, it was found that 2-ME inhibited ML-1 growth both in vivo and in vitro. The 2-ME induced ROS in ML-1 may be related to the 2-ME induced cell cycle effect. The potential of using 2-ME for HCC treatment is worthy of further study.
|
|---|
