Simultaneous knock-down of Bcl-xL and Mcl-1 induces apoptosis in pancreatic cancer cells

2014 Fiscal Year Final Research Report

• Project/Area Number: 24592036
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Digestive surgery
• Research Institution: Nagoya City University
• Principal Investigator: TAKAHASHI Hiroki 名古屋市立大学, 医学(系)研究科(研究院), 講師 (30381792)
• Co-Investigator(Kenkyū-buntansha): MATSUO Yoichi 名古屋市立大学, 医学(系)研究科(研究院), 准教授 (40381800) ; HARA Masayasu 名古屋市立大学, 医学(系)研究科(研究院), 講師 (80528860) ; SATO Mikinori 名古屋市立大学, 医学(系)研究科(研究院), 講師 (20305551)
• Project Period (FY): 2012-04-01 – 2015-03-31
• Keywords: 膵臓癌 / アポトーシス / Bcl-2ファミリー蛋白 / RNA干渉

Outline of Final Research Achievements

Of all gastrointestinal carcinomas, pancreatic cancer (PaCa) has the most unfavorable prognosis. Anti-apoptotic members of the Bcl-2 protein family are often over-expressed in human cancers and are thought to mediate the resistance to chemotherapeutic drugs. Thus, a better understanding of the anti-apoptotic mechanisms and the development of potent and non-toxic strategies to overcome the pro-survival mechanisms in PaCa cells are of utmost importance to improve the outcome of PaCa patients.
In this reseach, we first showed that the expression and localization of anti-apoptotic Bcl-2 family proteins in PaCa cells. Then, we used siRNA targeting to Bcl-2, Bcl-xL, and Mcl-1 to confirm the importance of anti-apoptotic Bcl-2 family proteins in PaCa cell survival. Simultaneous knock-down of Bcl-xL and Mcl-1 induced apoptosis strongly through Bax/mitochondria pathway. These results suggest that Bcl-xL and Mcl-1, which are over-expressed in PaCa may be potential therapeutic targets.

Free Research Field

医歯薬学