Involvement of Phosphatidylinositol 3-Kinase/Akt Pathway in Gemcitabine-Induced Apoptosis-Like Cell Death in Insulinoma Cell Line INS-1

• Motoshige Hironori

  Division of Biochemistry, Department of Life Science, School of Pharmacy, Hokkaido Pharmaceutical University

• Oyama Kyohei

  Division of Biochemistry, Department of Life Science, School of Pharmacy, Hokkaido Pharmaceutical University

• Takahashi Kiyoshi

  Division of Biochemistry, Department of Life Science, School of Pharmacy, Hokkaido Pharmaceutical University

• Sakurai Koichi

  Division of Biochemistry, Department of Life Science, School of Pharmacy, Hokkaido Pharmaceutical University

抄録

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.

収録刊行物

• Ｂｉｏｌｏｇｉｃａｌ　＆　Ｐｈａｒｍａｃｅｕｔｉｃａｌ　Ｂｕｌｌｅｔｉｎ

  Ｂｉｏｌｏｇｉｃａｌ　＆　Ｐｈａｒｍａｃｅｕｔｉｃａｌ　Ｂｕｌｌｅｔｉｎ 35 (11), 1932-1940, 2012

  公益社団法人 日本薬学会

キーワード

• gemcitabine
• phosphatidylinositol 3-kinase pathway
• apoptosis
• pancreatic β cell

詳細情報

• CRID: 1390282679610150912
• NII論文ID: 130001872251
• NII書誌ID: AA10885497
• DOI: 10.1248/bpb.b12-00298
• COI: 1:STN:280:DC%2BC3s7gs1WrtQ%3D%3D
• ISSN: 13475215
• ISSN: 09186158
• NDL書誌ID: 024032771
• PubMed: 23123465
• Web Site: https://ndlsearch.ndl.go.jp/books/R000000004-I024032771
• Web Site: https://www.jstage.jst.go.jp/article/bpb/35/11/35_b12-00298/_pdf
• Web Site: https://search.jamas.or.jp/link/ui/2013125452
• 本文言語コード: en
• データソース種別:
  • JaLC
  • NDL
  • Crossref
  • PubMed
  • CiNii Articles
• 抄録ライセンスフラグ: 使用不可