Enhanced susceptibility to apoptosis of oral squamous cell carcinoma cells subjected to combined treatment with anticancer drugs and phosphatidylinositol 3-kinase inhibitors

  • Authors:
    • Masayasu Iwase
    • Sayaka Yoshiba
    • Makiko Uchid
    • Sayaka Takaoka
    • Yuji Kurihara
    • Daisuke Ito
    • Masashi Hatori
    • Satoru Shintani
  • View Affiliations

  • Published online on: November 1, 2007     https://doi.org/10.3892/ijo.31.5.1141
  • Pages: 1141-1147
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Abstract

The purpose of this study was to determine whether phosphatidylinositol 3-kinase (PI 3-K) inhibitors could modulate the apoptotic activity of the anticancer drugs cisplatin, 5-fluorouracil or docetaxel in an oral squamous cell carcinoma (OSCC) cell line, HSC-2. In preliminary experiments, cisplatin, 5-fluorouracil and docetaxel inhibited the proliferation of OSCC cells in a dose-dependent manner. We found that two PI 3-K inhibitors, wortmannin and LY294002, markedly suppressed the phosphorylation of Akt in OSCC cells. Treatment of OSCC cells with PI 3-K inhibitors significantly enhanced cisplatin-, 5-fluorouracil- or docetaxel-induced apoptosis. Caspase-3 and -9 inhibitors, but not a caspase-8 inhibitor, reduced anticancer drug-mediated apoptosis in PI 3-K inhibitor-treated OSCC cells, suggesting that the apoptotic pathway induced by the combination of anticancer drug therapy and PI 3-K inhibition may be functionally related to the intrinsic apoptotic pathway in OSCC cells. Expression of Bcl-2, cellular inhibitor of apoptosis protein-1 (cIAP-1), and X-linked IAP was down-regulated, and expression of Bax was up-regulated by PI 3-K inhibitors, while that of Bcl-xL, Bak and cIAP-2 was not attenuated. We also found that Bad phosphorylation was down-regulated by PI 3-K inhibitors. These results suggested that inhibition of PI 3-K enhances the susceptibility of OSCC cells to anticancer drug-mediated apoptosis through regulation of expression and post-translational modification of both pro- and anti-apoptotic proteins. These findings could potentially lead to new strategies for improving the efficacy of anticancer drugs in OSCC cells.

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November 2007
Volume 31 Issue 5

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

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APA
Iwase, M., Yoshiba, S., Uchid, M., Takaoka, S., Kurihara, Y., Ito, D. ... Shintani, S. (2007). Enhanced susceptibility to apoptosis of oral squamous cell carcinoma cells subjected to combined treatment with anticancer drugs and phosphatidylinositol 3-kinase inhibitors. International Journal of Oncology, 31, 1141-1147. https://doi.org/10.3892/ijo.31.5.1141
MLA
Iwase, M., Yoshiba, S., Uchid, M., Takaoka, S., Kurihara, Y., Ito, D., Hatori, M., Shintani, S."Enhanced susceptibility to apoptosis of oral squamous cell carcinoma cells subjected to combined treatment with anticancer drugs and phosphatidylinositol 3-kinase inhibitors". International Journal of Oncology 31.5 (2007): 1141-1147.
Chicago
Iwase, M., Yoshiba, S., Uchid, M., Takaoka, S., Kurihara, Y., Ito, D., Hatori, M., Shintani, S."Enhanced susceptibility to apoptosis of oral squamous cell carcinoma cells subjected to combined treatment with anticancer drugs and phosphatidylinositol 3-kinase inhibitors". International Journal of Oncology 31, no. 5 (2007): 1141-1147. https://doi.org/10.3892/ijo.31.5.1141