Zoledronic acid increases the antitumor effect of gefitinib treatment for non-small cell lung cancer with EGFR mutations

  • Authors:
    • Chengjun Feng
    • Xiaoke Liu
    • Xiaoyu Li
    • Fuchun Guo
    • Chuying Huang
    • Qing Qin
    • Yongsheng Wang
  • View Affiliations

  • Published online on: April 13, 2016     https://doi.org/10.3892/or.2016.4741
  • Pages: 3460-3470
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Abstract

Non-small cell lung cancer (NSCLC) patients with epithelial growth factor receptor (EGFR) mutations and bone metastases are often concurrently administered tyrosine kinase inhibitors (TKIs) and bisphosphonates. Yet, the effects and mechanisms of these agents are unclear. In the present study, we aimed to ascertain whether zoledronic acid (ZA) increases the antitumor effects of gefitinib treatment on NSCLC with EGFR mutations and the related mechanisms of action. The effects of ZA and gefitinib on NSCLC tumor cells with EGFR mutations (HCC827, HCC827 GR and H1975) in regards to proliferation, apoptosis, cell cycle and signaling pathways were detected. ZA increased the antitumor effects of gefitinib on NSCLC with EGFR activating mutations and TKI resistance in vitro. Gefitinib caused cell cycle arrest in the G0/G1 phase, ZA induced S phase accumulation and the effect of the combined treatment was neutralization. Combined treatment obviously inhibited STAT3 and/or p‑STAT3 protein expression compared with treatment with each single drug in vitro and in vivo, and it also significantly inhibited TKI resistance NSCLC tumor growth in vivo. In conclusion, ZA increased the antitumor effects of gefitinib on NSCLC with EGFR activating mutations and TKI resistance by regulating the cell cycle, inducing caspase-3 expression and inhibiting STAT3 expression.
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June-2016
Volume 35 Issue 6

Print ISSN: 1021-335X
Online ISSN:1791-2431

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Spandidos Publications style
Feng C, Liu X, Li X, Guo F, Huang C, Qin Q and Wang Y: Zoledronic acid increases the antitumor effect of gefitinib treatment for non-small cell lung cancer with EGFR mutations. Oncol Rep 35: 3460-3470, 2016
APA
Feng, C., Liu, X., Li, X., Guo, F., Huang, C., Qin, Q., & Wang, Y. (2016). Zoledronic acid increases the antitumor effect of gefitinib treatment for non-small cell lung cancer with EGFR mutations. Oncology Reports, 35, 3460-3470. https://doi.org/10.3892/or.2016.4741
MLA
Feng, C., Liu, X., Li, X., Guo, F., Huang, C., Qin, Q., Wang, Y."Zoledronic acid increases the antitumor effect of gefitinib treatment for non-small cell lung cancer with EGFR mutations". Oncology Reports 35.6 (2016): 3460-3470.
Chicago
Feng, C., Liu, X., Li, X., Guo, F., Huang, C., Qin, Q., Wang, Y."Zoledronic acid increases the antitumor effect of gefitinib treatment for non-small cell lung cancer with EGFR mutations". Oncology Reports 35, no. 6 (2016): 3460-3470. https://doi.org/10.3892/or.2016.4741