| Summary: | 碩士 === 中國醫藥大學 === 醫學研究所 === 92 === Cancer is the leading cause of death in our country. Amongst all kinds of cancers, lung cancer is currently the one with the highest mortality. Therefore, it is important to explore the new anti-cancer drugs and improve therapeutic strategies for lung cancer treatment. In this thesis, we studied one of the newly synthesized 3΄,6,7-substituted 2-phenyl-4-quinolones compounds from Dr. Kuo Sheng-Chu that has been reported to inhibit tubulin polymerization and be cytotoxic to cancer cell lines. Among them, compound 3΄-Methoxy-6 pyrrolinyl- 2-phenyl-4-quinolone (K3) was found to be the most potent one. Human lung cancer cell CH27 was used to investigate anti-cancer effects of K3 on cell proliferation, cell cycle progression, and induction of apoptosis. This current study found that K3 was cytotoxic to human lung cancer cell with IC50 at 10 nM approximately. Cell cycle analysis demonstrated that 24 hours-K3-treated CH27 were mainly arrested at the G2/M phase. Afterward, sub-G1 population gradually increased with time. Within 72 hours of treatment, K3 induced a time dependent generation of typical DNA-laddering and apoptosis- specific morphological changes by DNA gel electrophoresis, Giemsa and DAPI staining, and TUNEL assay. Furthermore, immuno-fluorescence staining demonstrated the significant increase of Caspase-3 and the inhibition of tubulin polymerization after K3 treatment. Western blotting revealed that K3 induced the increase of Cyclin B after 24 hours of treatment. However protein levels of Cyclin A and CDK1 were decreased. The expression of anti-apoptotic Bcl-2 was decreased but the pro-apoptotic Bad was increased. Analysis from flow cytometry indicated that the mitochondria membrane potential was decreased and the amount of ROS (reactive-oxygen species) was increased. These results indicated that the ability of K3 to inhibit cancer cell is mainly mediated by the induction of G2/M arrest and apoptosis.
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