2015 Fiscal Year Final Research Report
Restoration of immune susceptibility to cancer cells regulated by autophagy and hypoxic responses
Project/Area Number |
25430150
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Research Category |
Grant-in-Aid for Scientific Research (C)
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Allocation Type | Multi-year Fund |
Section | 一般 |
Research Field |
Tumor therapeutics
|
Research Institution | Shimane University |
Principal Investigator |
|
Project Period (FY) |
2013-04-01 – 2016-03-31
|
Keywords | 低酸素 / 癌 / 免疫 / 治療抵抗性 / オートファジー |
Outline of Final Research Achievements |
In the human pancreatic cancer cells which showed resistance to tumor necrosis factor-related apoptosis-inducing ligand (TRAIL), as an anticancer drug, I investigated to restore the sensitivity to TRAIL and elucidate its cellular mechanisms. Pifithrin-mu, an inhibitor of autophagy or ABT-263, a Bcl-2 family inhibitor which targets Bcl-2, Bcl-xL, and Bcl-w significantly enhanced the sensitivity to TRAIL in human pancreatic cancer cells. Knockdown of HIF-2alpha, but not HIF-1alpha, using siRNA increased the susceptibility of pancreatic cancer cells to TRAIL via decreased the expression of anti-apoptotic protein survivin, and induced antitumor effects. These results suggest that inhibition of HIF-2alpha, autophagy, or anti-apoptotic molecules can enhance the efficacy of immune therapies to cancers.
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Free Research Field |
腫瘍免疫学
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