2015 Fiscal Year Final Research Report
Establishment of novel drug therapy targetting Warburg effect in gastric cancer
| Project/Area Number |
25462025
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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 |
Digestive surgery
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| Research Institution | Saga University |
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Principal Investigator |
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| Co-Investigator(Kenkyū-buntansha) |
NAKAMURA Jun 佐賀大学, 医学部, 助教 (60404175)
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| Project Period (FY) |
2013-04-01 – 2016-03-31
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| Keywords | HIF-1α / 胃癌 / ワールブルグ効果 / グルコース / インスリン / 活性酸素 / アポトーシス |
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| Outline of Final Research Achievements |
Hypoxia is substantial in solid tumors. Cancer cells under hypoxic environment are known to increase malignant characters including matastasis and drug resistance. Present study revealed that HIF-1α knockdown (KD) destroyed Warburg effect in gastric cancer cell line 58As9 under hypoxia, and induced apoptosis owing to excessive ROS production. Glucose (G) plus Insulin (I) treatment enhanced the apoptotic effect in the hypoxic 58As9 KD cells due to further ROS production. In vivo study showed that GI treatment increased apoptotic cells of 58As9 KD tumor, but not 58As9 control in nude mice, supporting in vitro data.
These results was successfully published in PLoS One paper in 2015. Thereafter, we isolated HIF-1α inhibitor YC-1 and revealed that YC-1 + GI therapy induced apoptotic effect in wild type 58As9 cells under hypoxia. At present, we are investigating whether or not YC-1 + GI therapy provides apoptotic effect on 58As9 tumor in nude mice.
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| Free Research Field |
胃癌の分子生物学
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