| Summary: | 碩士 === 國立中興大學 === 生物醫學研究所 === 101 === Colon cancer is the third leading cause of cancer mortality in Taiwan. Metfomin is a widely used drug to treat type II diabetes. A number of epidemiological studies have demonstrated that patients taking metfomin shows substantially lower cancer incidence and mortality than those not receiving this agent, but studies about the effect of metformin on the incidence and treatment efficacy of colon cancer are limited. Using human colon adenocarcinoma cell lines HT-29, HCT116 and SW620 as the cellular model, in this study we found that metfomin treatment led to inhibition of cell colony formation and cell viability, induction of cell cycle arrest at G1, and down-regulation of cyclin D1, CDK4, CDK6, SKP2, p27KIP1 and p21CIP1 in all cell lines examined. It is known that two signaling pathways leading to the G1 arrest, namely, the SKP2-p27KIP1 pathway and the, cyclin D-CDK4/6 pathway. We found that overexpression of SKP2 and knockdown of p27KIP1 protein in HT29 or HCT116 cells showed limited effect to rescue cells from metformin-induced repression of colony formation, suggesting that the SKP2-p27KIP1 pathway does not appear to be important for metformin-induced anti-colon cancer effect and thus implicating a potential role of the cyclin D-CDK4/6 pathway in this process. Additionally, we found that metformin induced apoptosis in SW620 cells, suggesting an additional mechanism underlying the anti-colon cancer effect of metformin.
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