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Article

A novel strategy of EGFR‑TKI combined chemotherapy in the treatment of human lung cancer with EGFR‑sensitive mutation

  • Authors:
    • Lanlin Zhang
    • Yuan Qi
    • Kailin Xing
    • Song Qian
    • Ping Zhang
    • Xianghua Wu
  • View Affiliations / Copyright

    Affiliations: Department of Medical Oncology, Fudan University Shanghai Cancer Center, Shanghai 200032, P.R. China, Department of Medical Oncology, Fudan University Shanghai Cancer Center, Shanghai 200032, P.R. China, Cancer Research Institute of Fudan University Shanghai Cancer Center, Shanghai 200032, P.R. China
  • Pages: 1046-1054
    |
    Published online on: June 18, 2018
       https://doi.org/10.3892/or.2018.6499
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Abstract

The discovery of epidermal growth factor receptor (EGFR)‑sensitive mutations in non‑small cell lung cancer (NSCLC) and the successful clinical application of EGFR tyrosine kinase inhibitors (TKIs) have changed the regimen of lung cancer therapy from traditional cytotoxic chemotherapy to molecular‑targeted cancer therapy. However, the main limitation of EGFR‑TKI therapy is the heterogeneity of lung cancer harboring EGFR‑sensitive mutations. In addition, the synergistic effect of the administration of chemotherapy and EGFR‑TKIs, combined with tumor heterogeneity, on NSCLC remains unclear. The present study aimed to investigate the optimal schedule for combined treatment with paclitaxel/gemcitabine and gefitinib in co‑cultured NSCLC cell lines, in which PC9 cells were mixed with A549 cells at 0:1, 1:19, 1:3, 1:1, 3:1 and 1:0 ratios, and clarified the associated mechanisms. The mixed cells were used to simulate the tumor heterogeneity in the human cancer environment and to define the differential anti‑proliferative effects of nine schedules of paclitaxel/gemcitabine and gefitinib, based on cell cycle distribution. We confirmed that gefitinib arrested PC9 cell growth, mainly at the G1 phase, at 24 h regardless of low or high concentration. After a 24‑h culture in gefitinib‑free medium, the cell cycle returned to its normal state. Paclitaxel and gemcitabine induced G2/M phase and S phase arrest at 72 h, respectively. The anti‑proliferative effect of paclitaxel/gemcitabine followed by gefitinib resulted in the optimum anti‑proliferative activity compared with the other seven schedules, which was not affected by tumor heterogeneity. Cell cycle‑dependent synergism may contribute to this effect. Our results are in accordance with most of the existing clinical trials, and could provide a potential treatment option for patients with advanced NSCLC and for the ongoing clinical investigation of the sequential treatment of NSCLC.
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Copy and paste a formatted citation
Spandidos Publications style
Zhang L, Qi Y, Xing K, Qian S, Zhang P and Wu X: A novel strategy of EGFR‑TKI combined chemotherapy in the treatment of human lung cancer with EGFR‑sensitive mutation. Oncol Rep 40: 1046-1054, 2018.
APA
Zhang, L., Qi, Y., Xing, K., Qian, S., Zhang, P., & Wu, X. (2018). A novel strategy of EGFR‑TKI combined chemotherapy in the treatment of human lung cancer with EGFR‑sensitive mutation. Oncology Reports, 40, 1046-1054. https://doi.org/10.3892/or.2018.6499
MLA
Zhang, L., Qi, Y., Xing, K., Qian, S., Zhang, P., Wu, X."A novel strategy of EGFR‑TKI combined chemotherapy in the treatment of human lung cancer with EGFR‑sensitive mutation". Oncology Reports 40.2 (2018): 1046-1054.
Chicago
Zhang, L., Qi, Y., Xing, K., Qian, S., Zhang, P., Wu, X."A novel strategy of EGFR‑TKI combined chemotherapy in the treatment of human lung cancer with EGFR‑sensitive mutation". Oncology Reports 40, no. 2 (2018): 1046-1054. https://doi.org/10.3892/or.2018.6499
Copy and paste a formatted citation
x
Spandidos Publications style
Zhang L, Qi Y, Xing K, Qian S, Zhang P and Wu X: A novel strategy of EGFR‑TKI combined chemotherapy in the treatment of human lung cancer with EGFR‑sensitive mutation. Oncol Rep 40: 1046-1054, 2018.
APA
Zhang, L., Qi, Y., Xing, K., Qian, S., Zhang, P., & Wu, X. (2018). A novel strategy of EGFR‑TKI combined chemotherapy in the treatment of human lung cancer with EGFR‑sensitive mutation. Oncology Reports, 40, 1046-1054. https://doi.org/10.3892/or.2018.6499
MLA
Zhang, L., Qi, Y., Xing, K., Qian, S., Zhang, P., Wu, X."A novel strategy of EGFR‑TKI combined chemotherapy in the treatment of human lung cancer with EGFR‑sensitive mutation". Oncology Reports 40.2 (2018): 1046-1054.
Chicago
Zhang, L., Qi, Y., Xing, K., Qian, S., Zhang, P., Wu, X."A novel strategy of EGFR‑TKI combined chemotherapy in the treatment of human lung cancer with EGFR‑sensitive mutation". Oncology Reports 40, no. 2 (2018): 1046-1054. https://doi.org/10.3892/or.2018.6499
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