Dexamethasone interferes with trastuzumab-induced cell growth inhibition through restoration of AKT activity in BT-474 breast cancer cells

  • Authors:
    • Takashi Sumikawa
    • Yasushi Shigeoka
    • Tadashi Igishi
    • Hisashi Suyama
    • Akira Yamasaki
    • Kiyoshi Hashimoto
    • Shingo Matsumoto
    • Kenichi Takeda
    • Yasuto Ueda
    • Eiji Shimizu
  • View Affiliations

  • Published online on: March 1, 2008     https://doi.org/10.3892/ijo.32.3.683
  • Pages: 683-688
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Abstract

The combination of trastuzumab with paclitaxel (PTX) is an important option for the treatment of HER2-positive breast cancer. Dexamethasone (Dex) premedication is routinely used in the treatment with PTX. The interactions among Dex, PTX and trastuzumab were evaluated in BT-474 cells. Dex interfered with trastuzumab-induced cell growth inhibition without clear effects on PTX-induced cytotoxicity. Trastuzumab dephosphorylated retinoblastoma protein (pRB). Dex restored this trastuzumab-induced dephosphorylation of pRB and released trastuzumab-induced G1 arrest. Trastuzumab suppressed AKT activity without affecting ERK activity. A specific inhibitor for the phosphatidylinositol 3-kinase/AKT pathway, LY294002, inhibited cell growth and AKT and pRB phosphorylation. Dex restored the trastuzumab-induced suppression of AKT without affecting ERK activity. It was concluded that Dex interferes with trastuzumab-induced cell growth inhibition, at least partially, through the restoration of trastuzumab-induced AKT suppression and subsequent pRB dephosphorylation in BT-474 breast cancer cells. These observations support the development of new chemotherapeutic regimens without glucocorticoid premedication.

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March 2008
Volume 32 Issue 3

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

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Spandidos Publications style
Sumikawa T, Shigeoka Y, Igishi T, Suyama H, Yamasaki A, Hashimoto K, Matsumoto S, Takeda K, Ueda Y, Shimizu E, Shimizu E, et al: Dexamethasone interferes with trastuzumab-induced cell growth inhibition through restoration of AKT activity in BT-474 breast cancer cells. Int J Oncol 32: 683-688, 2008.
APA
Sumikawa, T., Shigeoka, Y., Igishi, T., Suyama, H., Yamasaki, A., Hashimoto, K. ... Shimizu, E. (2008). Dexamethasone interferes with trastuzumab-induced cell growth inhibition through restoration of AKT activity in BT-474 breast cancer cells. International Journal of Oncology, 32, 683-688. https://doi.org/10.3892/ijo.32.3.683
MLA
Sumikawa, T., Shigeoka, Y., Igishi, T., Suyama, H., Yamasaki, A., Hashimoto, K., Matsumoto, S., Takeda, K., Ueda, Y., Shimizu, E."Dexamethasone interferes with trastuzumab-induced cell growth inhibition through restoration of AKT activity in BT-474 breast cancer cells". International Journal of Oncology 32.3 (2008): 683-688.
Chicago
Sumikawa, T., Shigeoka, Y., Igishi, T., Suyama, H., Yamasaki, A., Hashimoto, K., Matsumoto, S., Takeda, K., Ueda, Y., Shimizu, E."Dexamethasone interferes with trastuzumab-induced cell growth inhibition through restoration of AKT activity in BT-474 breast cancer cells". International Journal of Oncology 32, no. 3 (2008): 683-688. https://doi.org/10.3892/ijo.32.3.683