Discovery of MET-inducing compounds as anti-cancer chemotherapeutic agents

2016 Fiscal Year Final Research Report

• Project/Area Number: 26350974
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Chemical biology
• Research Institution: Keio University
• Principal Investigator: Tashiro Etsu 慶應義塾大学, 理工学部(矢上), 講師 (00365446)
• Co-Investigator(Renkei-kenkyūsha): IMOTO MASAYA 慶應義塾大学, 理工学部, 教授 (60213253)
• Project Period (FY): 2014-04-01 – 2017-03-31
• Keywords: EMT / 制がん剤耐性 / シスプラチン / TGF-beta

Outline of Final Research Achievements

There are now growing evidences suggesting an association between EMT, a hallmark of tumor malignancy, and chemoresistance to many cytotoxic drugs. However, it has not been fully clear about its mechanism. Here, we established cisplatin-resistant clones of human colorectal carcinoma LoVo cells (CDDPr/LoVo cells) by continuously exposing LoVo cells to cisplatin and we found that EMT was induced in CDDPr/LoVo cells. Thus, we performed chemical genomics approach to address the mechanism by which EMT was induced in CDDPr/LoVo cells. As a result, we found that the secretion of TGF-β in CDDPr/LoVo cells was elevated compared to that in LoVo cells. Moreover, when cisplatin was treated with LoVo cells, the secretion of TGF-β was enhanced within a few days after cisplatin treatment, which resulted in EMT induction. Since mesenchymal cells were resistance against cisplatin-induced apoptosis, it is likely that cisplatin-induced EMT by TGF-β secretion contributes to acquire the chemoresistance.

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