Involvement of Phosphatidylinositol 3-Kinase/Akt Pathway in Gemcitabine-Induced Apoptosis-Like Cell Death in Insulinoma Cell Line INS-1
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- Motoshige Hironori
- Division of Biochemistry, Department of Life Science, School of Pharmacy, Hokkaido Pharmaceutical University
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- Oyama Kyohei
- Division of Biochemistry, Department of Life Science, School of Pharmacy, Hokkaido Pharmaceutical University
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- Takahashi Kiyoshi
- Division of Biochemistry, Department of Life Science, School of Pharmacy, Hokkaido Pharmaceutical University
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- Sakurai Koichi
- Division of Biochemistry, Department of Life Science, School of Pharmacy, Hokkaido Pharmaceutical University
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Abstract
This study demonstrated gemcitabine-induced cytotoxicity in the insulinoma cell line INS-1. Gemcitabine inhibited INS-1 cell proliferation and maintained consistent cell number for 24 h, and then caused apoptosis within 48 h of incubation. Since gemcitabine activates the phosphatidylinositol 3-kinase (PI3-K)/Akt pathway, which is involved in the resistance of pancreatic exocrine cancer to gemcitabine, we investigated the participation of this pathway in gemcitabine-induced cytotoxicity in INS-1 cells. LY294002 and wortmannin, two PI3-K inhibitors, significantly prevented gemcitabine-induced cytotoxicity in INS-1 cells, indicating that the PI3-K/Akt pathway is involved in gemcitabine-induced cytotoxicity. Gemcitabine-induced Akt phosphorylation in INS-1 cells was prevented by LY294002. Although gemcitabine induced cell cycle arrest at the G1 and early S phases, LY294002 did not inhibit the cell cycle. These data suggest that PI3-K activation does not influence gemcitabine-induced cell cycle arrest. In gemcitabine-treated cells, nuclear fragmentation and DNA ladder formation were observed. These findings suggest that gemcitabine induced apoptotic cell death in INS-1 cells through the activation of the PI3-K/Akt pathway.
Journal
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- Biological and Pharmaceutical Bulletin
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Biological and Pharmaceutical Bulletin 35 (11), 1932-1940, 2012
The Pharmaceutical Society of Japan
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Details 詳細情報について
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- CRID
- 1390282679610150912
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- NII Article ID
- 130001872251
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- NII Book ID
- AA10885497
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- COI
- 1:STN:280:DC%2BC3s7gs1WrtQ%3D%3D
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- ISSN
- 13475215
- 09186158
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- NDL BIB ID
- 024032771
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- PubMed
- 23123465
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- Text Lang
- en
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- Data Source
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- JaLC
- NDL
- Crossref
- PubMed
- CiNii Articles
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- Abstract License Flag
- Disallowed