Dexamethasone inhibits paclitaxel-induced cytotoxic activity through retinoblastoma protein dephosphorylation in non-small cell lung cancer cells

Morita,Masato; Suyama,Hisashi; Igishi,Tadashi; Shigeoka,Yasushi; Kodani,Masahiro; Hashimoto,Kiyoshi; Takeda,Kenichi; Sumikawa,Takashi; Shimizu,Eiji

doi:10.3892/ijo.30.1.187

January 2007 Volume 30 Issue 1

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January 2007 Volume 30 Issue 1

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Article

Dexamethasone inhibits paclitaxel-induced cytotoxic activity through retinoblastoma protein dephosphorylation in non-small cell lung cancer cells

Authors:
- Masato Morita
- Hisashi Suyama
- Tadashi Igishi
- Yasushi Shigeoka
- Masahiro Kodani
- Kiyoshi Hashimoto
- Kenichi Takeda
- Takashi Sumikawa
- Eiji Shimizu
View Affiliations / Copyright

Affiliations: Division of Medical Oncology and Molecular Respirology, Faculty of Medicine, Tottori University, Yonago 683-8504, Japan
Pages: 187-192
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Published online on: January 1, 2007

https://doi.org/10.3892/ijo.30.1.187
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Abstract

Paclitaxel is used frequently for the treatment of patients with non-small cell lung cancer. Hypersensitivity reactions remain one of the major adverse events in the clinical use of paclitaxel. Glucocorticoids are used to prevent these adverse events. This study was carried out in order to clarify the effect of glucocorticoids on paclitaxel-induced cytotoxity of cancer cells. Pretreatment with 10 µM of dexamethasone inhibited ERK activation and subsequent retinoblastoma protein (pRB) phosphorylation, and reduced sensitivity to paclitaxel in A549 cells. Then, we utilized ERK (PD98059) and AKT (LY294002) inhibitors. PD98059 and LY294002 effectively suppressed pRB phosphorylation in A549 cells. Dexamethasone (10 µM) suppressed ERK activity as well as PD98059, although it did not affect AKT activity. Furthermore, the combinations of paclitaxel with PD98059 or LY294002 were similarly antagonistic. Our observation in this study raised the possibility that dexamethasone pretreatment antagonizes paclitaxel-induced cytotoxicity through ERK suppression and pRB dephosphorylation. These observations support the development of new generation taxane-based chemotherapy without glucocorticoid premedication.

Journals

International Journal of Molecular Medicine

International Journal of Oncology

Molecular Medicine Reports

Oncology Reports

Experimental and Therapeutic Medicine

Oncology Letters

Biomedical Reports

Molecular and Clinical Oncology

World Academy of Sciences Journal

International Journal of Functional Nutrition

International Journal of Epigenetics

Medicine International

Dexamethasone inhibits paclitaxel-induced cytotoxic activity through retinoblastoma protein dephosphorylation in non-small cell lung cancer cells

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