Discovery of MET-inducing compounds as anti-cancer chemotherapeutic agents
| Project/Area Number |
26350974
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| Research Category |
Grant-in-Aid for Scientific Research (C)
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| Allocation Type | Multi-year Fund |
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| Section | 一般 |
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| Research Field |
Chemical biology
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| Research Institution | Keio University |
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Principal Investigator |
Tashiro Etsu 慶應義塾大学, 理工学部(矢上), 講師 (00365446)
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| Co-Investigator(Renkei-kenkyūsha) |
IMOTO MASAYA 慶應義塾大学, 理工学部, 教授 (60213253)
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| Project Period (FY) |
2014-04-01 – 2017-03-31
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| Project Status |
Completed (Fiscal Year 2016)
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| Budget Amount *help |
¥4,810,000 (Direct Cost: ¥3,700,000、Indirect Cost: ¥1,110,000)
Fiscal Year 2016: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000)
Fiscal Year 2015: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
Fiscal Year 2014: ¥1,950,000 (Direct Cost: ¥1,500,000、Indirect Cost: ¥450,000)
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| Keywords | EMT / 制がん剤耐性 / シスプラチン / TGF-beta / 上皮間葉転換 / カドヘリン / 薬剤感受性 |
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| 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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Report
(4 results)
Research Products
(21 results)
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[Journal Article] Protein kinase A inhibition facilitates the antitumor activity of xanthohumol, a valosin-containing protein inhibitor2017
Author(s)
Y. Shikata Y, T. Yoshimaru, M. Komatsu, H. Katoh, R. Sato, S. Kanagaki, Y. Okazaki, S. Toyokuni, E. Tashiro, S. Ishikawa, T. Katagiri, M. Imoto,
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Journal Title
Cancer Science
Volume: 108
Issue: 4
Pages: 785-794
DOI
NAID
Related Report
Peer Reviewed / Open Access
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