A novel dual PI3Kα/mTOR inhibitor PI-103 with high antitumor activity in non-small cell lung cancer cells

  • Authors:
    • Zu-Quan Zou
    • Xiao-Hong Zhang
    • Feng Wang
    • Qi-Jun Shen
    • Jin Xu
    • Li-Na Zhang
    • Wen-Hua Xing
    • Ren-Jie Zhuo
    • Duo Li
  • View Affiliations

  • Published online on: July 1, 2009     https://doi.org/10.3892/ijmm_00000212
  • Pages: 97-101
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Abstract

PI-103, the first synthetic multitargeted compound which simultaneously inhibits PI3Kα and mammalian target of rapamycin (mTOR) shows high antitumor activity in glioma xenografts. In the present study, clear antitumor activity was observed with PI-103 treatment in two gefitinib-resistant non-small cell lung cancer (NSCLC) cell lines, A549 and H460, by simultaneously inhibiting p70s6k phosporylation and Akt phosphorylation in response to mTOR inhibition. In addition, H460 cells with activating mutations of PIK3CA were more sensitive to PI-103 than A549 cells with wild-type PIK3CA. PI-103 was found to inhibit growth by causing G0-G1 arrest in A549 and H460 cells. Western blotting showed that PI-103 induced down-regulation of cyclin D1 and E1 and simultaneously up-regulated p21 and p27, associated with arrest in the G0-G1 phase of the cell cycle. Furthermore, p53, the tumor suppressor which transcriptionally regulates p21, was also upregulated with PI-103 treatment. Collectively, our results suggest that multitargeted intervention is the most effective tumor therapy, and the cooperative blockade of PI3Kα and mTOR with PI-103 shows promise for treating gefitinib-resistant NSCLC.

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July 2009
Volume 24 Issue 1

Print ISSN: 1107-3756
Online ISSN:1791-244X

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Spandidos Publications style
Zou Z, Zhang X, Wang F, Shen Q, Xu J, Zhang L, Xing W, Zhuo R and Li D: A novel dual PI3Kα/mTOR inhibitor PI-103 with high antitumor activity in non-small cell lung cancer cells. Int J Mol Med 24: 97-101, 2009.
APA
Zou, Z., Zhang, X., Wang, F., Shen, Q., Xu, J., Zhang, L. ... Li, D. (2009). A novel dual PI3Kα/mTOR inhibitor PI-103 with high antitumor activity in non-small cell lung cancer cells. International Journal of Molecular Medicine, 24, 97-101. https://doi.org/10.3892/ijmm_00000212
MLA
Zou, Z., Zhang, X., Wang, F., Shen, Q., Xu, J., Zhang, L., Xing, W., Zhuo, R., Li, D."A novel dual PI3Kα/mTOR inhibitor PI-103 with high antitumor activity in non-small cell lung cancer cells". International Journal of Molecular Medicine 24.1 (2009): 97-101.
Chicago
Zou, Z., Zhang, X., Wang, F., Shen, Q., Xu, J., Zhang, L., Xing, W., Zhuo, R., Li, D."A novel dual PI3Kα/mTOR inhibitor PI-103 with high antitumor activity in non-small cell lung cancer cells". International Journal of Molecular Medicine 24, no. 1 (2009): 97-101. https://doi.org/10.3892/ijmm_00000212