Investigation of Therapeutic Drugs Targeting Eps8 for Colorectal Cancer Treatment

• Main Authors: CremildaLai, 賴啟楹
• Other Authors: Tzeng-Horng Leu
• Format: Others
• Language: en_US
• Published: 2015
• Online Access: http://ndltd.ncl.edu.tw/handle/31300061197120178665

碩士 === 國立成功大學 === 藥理學研究所 === 103 === Colorectal cancer is the third most common cancer in the world. It has been reported that Eps8, epidermal growth factor receptor pathway substrate 8, is expressed at elevated levels in colon cancer and high levels of Eps8 results in poor prognosis of cancer patients. Eps8 acts as an oncoprotein in human cancer. Therefore, an agent that attenuates Eps8 expression can be developed to be therapeutic drug for colon cancer. The aim of this study is to investigate the underlying mechanisms of M9, a potential Eps8 inhibitor for the treatment of colon cancer. Through connectivity map, which includes 6100 drug-mediated expression profiles, 11 candidate drugs were shown to have anti-correlated expression patterns of Eps8. Human colon cancer cell lines Ht-29, SW480 and SW620 were used as model in this study. Results from cell viability assay determined that M9, one of the 11 candidate drugs, inhibited cell proliferation of the treated cells. Then we validated that M9 inhibited eps8 gene transcription through RT-PCR. Moreover, results from western blot analysis revealed that M9 suppressed the expression of Eps8, the activity of FAK and Src and the expression of FAK and Src in dose- and time- dependent manner. In addition, in the flow cytometry analysis, M9 resulted in G1 phase arrest in the colon cancer cell lines and affecting cell proliferation. These findings indicate that M9 is an Eps8 inhibitor and can inhibit cancer cell growth, suggesting its repositioning potential for colon cancer treatment.