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

  • Published online on: January 1, 2007     https://doi.org/10.3892/ijo.30.1.187
  • Pages: 187-192
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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.

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January 2007
Volume 30 Issue 1

Print ISSN: 1019-6439
Online ISSN:1791-2423

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Spandidos Publications style
Morita M, Suyama H, Igishi T, Shigeoka Y, Kodani M, Hashimoto K, Takeda K, Sumikawa T and Shimizu E: Dexamethasone inhibits paclitaxel-induced cytotoxic activity through retinoblastoma protein dephosphorylation in non-small cell lung cancer cells. Int J Oncol 30: 187-192, 2007
APA
Morita, M., Suyama, H., Igishi, T., Shigeoka, Y., Kodani, M., Hashimoto, K. ... Shimizu, E. (2007). Dexamethasone inhibits paclitaxel-induced cytotoxic activity through retinoblastoma protein dephosphorylation in non-small cell lung cancer cells. International Journal of Oncology, 30, 187-192. https://doi.org/10.3892/ijo.30.1.187
MLA
Morita, M., Suyama, H., Igishi, T., Shigeoka, Y., Kodani, M., Hashimoto, K., Takeda, K., Sumikawa, T., Shimizu, E."Dexamethasone inhibits paclitaxel-induced cytotoxic activity through retinoblastoma protein dephosphorylation in non-small cell lung cancer cells". International Journal of Oncology 30.1 (2007): 187-192.
Chicago
Morita, M., Suyama, H., Igishi, T., Shigeoka, Y., Kodani, M., Hashimoto, K., Takeda, K., Sumikawa, T., Shimizu, E."Dexamethasone inhibits paclitaxel-induced cytotoxic activity through retinoblastoma protein dephosphorylation in non-small cell lung cancer cells". International Journal of Oncology 30, no. 1 (2007): 187-192. https://doi.org/10.3892/ijo.30.1.187