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

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.

journal_name

Oncol Rep

journal_title

Oncology reports

authors

Feng C,Liu X,Li X,Guo F,Huang C,Qin Q,Wang Y

doi

10.3892/or.2016.4741

subject

Has Abstract

pub_date

2016-06-01 00:00:00

pages

3460-70

issue

6

eissn

1021-335X

issn

1791-2431

journal_volume

35

pub_type

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