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PI3K inhibition sensitizes EGFR wild‑type NSCLC cell lines to erlotinib chemotherapy

  • Authors:
    • Xin Zhou
    • Xiaowen Wang
    • Hongge Zhu
    • Guomin Gu
    • Yiyi Zhan
    • Chunling Liu
    • Gang Sun
  • View Affiliations / Copyright

    Affiliations: Department of Second Pulmonary Medicine, Affiliated Tumor Hospital of Xinjiang Medical University, Urumqi, Xinjiang 830011, P.R. China, Department of Second Breast Surgery, Affiliated Tumor Hospital of Xinjiang Medical University, Urumqi, Xinjiang 830011, P.R. China, Department of Breast, Head and Neck Surgery, Affiliated Tumor Hospital of Xinjiang Medical University, Urumqi, Xinjiang 830011, P.R. China
    Copyright: © Zhou et al. This is an open access article distributed under the terms of Creative Commons Attribution License.
  • Article Number: 9
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    Published online on: November 4, 2020
       https://doi.org/10.3892/etm.2020.9441
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Abstract

Tyrosine kinase inhibitors (TKIs) bring significant benefits for patients with cancers harboring epidermal growth factor receptor (EGFR) mutations. However, after treatment for a certain period, most patients ultimately acquire resistance. Numerous studies indicated that PI3K has an important role in tumor cell growth and drug sensitivity. Furthermore, inhibition of PI3K may lead to sensitization of non‑small cell lung cancer (NSCLC) cells to EGFR‑TKIs. The aim of the present study was to explore whether LY294002, an inhibitor of PI3K, is able to improve the sensitivity of NSCLC cell lines with wild‑type EGFR to the EGFR‑TKI erlotinib. An MTT assay was used to examine the effect of combined treatment with LY294002 and erlotinib on cell survival of two EGFR wild‑type NSCLC cell lines, NCI‑H661 and NCI‑H460. Furthermore, flow cytometry was used to assess apoptosis in NCI‑H661 and NCI‑H460 cells after treatment with erlotinib and LY294002. In addition, the expression of downstream proteins was detected by western blot analysis. The results indicated that the number of viable NCI‑H661 and NCI‑H460 cells was dose‑dependently reduced by erlotinib or LY294002. Compared to treatment with erlotinib alone, the cell apoptosis was enhanced if combined treatment of erlotinib and LY294002 was performed in NCI‑H661 cells. Furthermore, combination treatment of erlotinib and LY294002 resulted in a significant reduction of phosphorylated p70S6K levels in NCI‑H661 [PI3K catalytic subunit alpha (PI3KCA) wild‑type] cells. However, this phenomenon was not observed in the NCI‑H460 cell line (PIK3CA mutant‑type). In conclusion, the present study indicated that inhibition of PI3K may have the potential to improve the sensitivity of NSCLC cells to an EGFR‑TKI. However, the therapeutic effect may depend on the mutation status of PIK3CA.
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Copy and paste a formatted citation
Spandidos Publications style
Zhou X, Wang X, Zhu H, Gu G, Zhan Y, Liu C and Sun G: PI3K inhibition sensitizes EGFR wild‑type NSCLC cell lines to erlotinib chemotherapy. Exp Ther Med 21: 9, 2021.
APA
Zhou, X., Wang, X., Zhu, H., Gu, G., Zhan, Y., Liu, C., & Sun, G. (2021). PI3K inhibition sensitizes EGFR wild‑type NSCLC cell lines to erlotinib chemotherapy. Experimental and Therapeutic Medicine, 21, 9. https://doi.org/10.3892/etm.2020.9441
MLA
Zhou, X., Wang, X., Zhu, H., Gu, G., Zhan, Y., Liu, C., Sun, G."PI3K inhibition sensitizes EGFR wild‑type NSCLC cell lines to erlotinib chemotherapy". Experimental and Therapeutic Medicine 21.1 (2021): 9.
Chicago
Zhou, X., Wang, X., Zhu, H., Gu, G., Zhan, Y., Liu, C., Sun, G."PI3K inhibition sensitizes EGFR wild‑type NSCLC cell lines to erlotinib chemotherapy". Experimental and Therapeutic Medicine 21, no. 1 (2021): 9. https://doi.org/10.3892/etm.2020.9441
Copy and paste a formatted citation
x
Spandidos Publications style
Zhou X, Wang X, Zhu H, Gu G, Zhan Y, Liu C and Sun G: PI3K inhibition sensitizes EGFR wild‑type NSCLC cell lines to erlotinib chemotherapy. Exp Ther Med 21: 9, 2021.
APA
Zhou, X., Wang, X., Zhu, H., Gu, G., Zhan, Y., Liu, C., & Sun, G. (2021). PI3K inhibition sensitizes EGFR wild‑type NSCLC cell lines to erlotinib chemotherapy. Experimental and Therapeutic Medicine, 21, 9. https://doi.org/10.3892/etm.2020.9441
MLA
Zhou, X., Wang, X., Zhu, H., Gu, G., Zhan, Y., Liu, C., Sun, G."PI3K inhibition sensitizes EGFR wild‑type NSCLC cell lines to erlotinib chemotherapy". Experimental and Therapeutic Medicine 21.1 (2021): 9.
Chicago
Zhou, X., Wang, X., Zhu, H., Gu, G., Zhan, Y., Liu, C., Sun, G."PI3K inhibition sensitizes EGFR wild‑type NSCLC cell lines to erlotinib chemotherapy". Experimental and Therapeutic Medicine 21, no. 1 (2021): 9. https://doi.org/10.3892/etm.2020.9441
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