Gamma-secretase complexes regulate the responses of human pancreatic ductal adenocarcinoma cells to taxanes

Takehiko Tasaka, Takashi Akiyoshi, Koji Yamaguchi, Masao Tanaka, Hideya Onishi, Mitsuo Katano

研究成果: ジャーナルへの寄稿記事

7 引用 (Scopus)

抄録

Background!Aim: It was previously reported that y-secretase inhibitors (GSIs) enhance taxane-induced mitotic arrest and apoptosis in colon cancer cells. To enable the development of taxane-based chemotherapy for pancreatic ductal adenocarcinoma (PDAC), this study investigated the molecular mechanisms by which y-secretase (GS) complexes regulate taxane sensitivity. Materials and Methods: The effect of GS complexes on taxane-induced apoptosis in PDAC cells was evaluated by a cell cycle analysis. GS complexes were examined with small interference RNAs targeted to GS complex-related genes. Results: GSIs and silencing of presenilin 1 (PS1) did not affect cell proliferation but resulted in enhanced taxane-induced G2IM accumulation and apoptosis. Silencing of the Notch gene did not induce these effects. However, PS2-specific silencing suppressed proliferation and taxane-induced apoptosis. Conclusion: Data from this study indicate that GS complexes regulate the response of PDAC to taxanes through GS-dependent and GS-independent mechanisms.

元の言語英語
ページ(範囲)4999-5010
ページ数12
ジャーナルAnticancer research
30
発行部数12
出版物ステータス出版済み - 12 1 2010

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Taxoids
Amyloid Precursor Protein Secretases
Adenocarcinoma
Apoptosis
Presenilin-1
Gene Silencing
RNA Interference
Colonic Neoplasms
taxane
Cell Cycle
Cell Proliferation
Drug Therapy
Genes

All Science Journal Classification (ASJC) codes

  • Oncology
  • Cancer Research

これを引用

Tasaka, T., Akiyoshi, T., Yamaguchi, K., Tanaka, M., Onishi, H., & Katano, M. (2010). Gamma-secretase complexes regulate the responses of human pancreatic ductal adenocarcinoma cells to taxanes. Anticancer research, 30(12), 4999-5010.

Gamma-secretase complexes regulate the responses of human pancreatic ductal adenocarcinoma cells to taxanes. / Tasaka, Takehiko; Akiyoshi, Takashi; Yamaguchi, Koji; Tanaka, Masao; Onishi, Hideya; Katano, Mitsuo.

:: Anticancer research, 巻 30, 番号 12, 01.12.2010, p. 4999-5010.

研究成果: ジャーナルへの寄稿記事

Tasaka, T, Akiyoshi, T, Yamaguchi, K, Tanaka, M, Onishi, H & Katano, M 2010, 'Gamma-secretase complexes regulate the responses of human pancreatic ductal adenocarcinoma cells to taxanes', Anticancer research, 巻. 30, 番号 12, pp. 4999-5010.
Tasaka, Takehiko ; Akiyoshi, Takashi ; Yamaguchi, Koji ; Tanaka, Masao ; Onishi, Hideya ; Katano, Mitsuo. / Gamma-secretase complexes regulate the responses of human pancreatic ductal adenocarcinoma cells to taxanes. :: Anticancer research. 2010 ; 巻 30, 番号 12. pp. 4999-5010.
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AU - Tasaka, Takehiko

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AU - Onishi, Hideya

AU - Katano, Mitsuo

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N2 - Background!Aim: It was previously reported that y-secretase inhibitors (GSIs) enhance taxane-induced mitotic arrest and apoptosis in colon cancer cells. To enable the development of taxane-based chemotherapy for pancreatic ductal adenocarcinoma (PDAC), this study investigated the molecular mechanisms by which y-secretase (GS) complexes regulate taxane sensitivity. Materials and Methods: The effect of GS complexes on taxane-induced apoptosis in PDAC cells was evaluated by a cell cycle analysis. GS complexes were examined with small interference RNAs targeted to GS complex-related genes. Results: GSIs and silencing of presenilin 1 (PS1) did not affect cell proliferation but resulted in enhanced taxane-induced G2IM accumulation and apoptosis. Silencing of the Notch gene did not induce these effects. However, PS2-specific silencing suppressed proliferation and taxane-induced apoptosis. Conclusion: Data from this study indicate that GS complexes regulate the response of PDAC to taxanes through GS-dependent and GS-independent mechanisms.

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