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Journal of Cancer Research and Clinical Oncology

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01-07-2020 | NSCLC | Original Article – Cancer Research

Gefitinib sensitization of cisplatin-resistant wild-type EGFR non-small cell lung cancer cells

Authors: Amin Li, Weiya Cao, Xueke Liu, Yinci Zhang, Yongfang Ma, Ruyue Xu, Rongbo Zhang, Xinkuang Liu, Shuping Zhou, Ruikai Wang, Jiachang Liu, Xiaolong Tang

Published in: Journal of Cancer Research and Clinical Oncology | Issue 7/2020

Abstract

Purpose

The usual first-line strategy of wild-type EGFR (wtEGFR) non-small cell lung cancer (NSCLC) remains cisplatin-based chemotherapy. However, cisplatin often loses effectiveness because most tumors acquire drug resistance over time. As EGFR is the most important pro-survival/proliferation signal receptor in NSCLC cells, we aimed at investigating whether cisplatin resistance is related to EGFR activation and further evaluating the combined effects of cisplatin/gefitinib (EGFR-tyrosine kinase inhibitor, EGFR-TKI) on cisplatin-resistant wtEGFR NSCLC cells.

Materials and methods

EGFR activation was analysed in parental and cisplatin-resistant wtEGFR NSCLC cell lines (H358 and H358^R, A549 and A549^R). Cellular proliferation and apoptosis of H358^R/A549^R cells treated with cisplatin or gefitinib, alone or in combination were investigated, and the related effector protein was detected by western blot analysis. Anti-tumor effect of two drugs combined was evaluated in animal models of H358^R xenografts in vivo.

Results

EGFR was significantly phosphorylated in cisplatin-resistant wtEGFR NSCLC cells H358^R and A549^R than their parental cells. In H358^R and A549^R cells, anti-proliferative ability of gefitinib was further improved, and gefitinib combined with cisplatin enhanced inhibition of cellular survive/proliferation, and promotion of apoptosis in vitro. The combined effects were also associated with the inhibition of EGFR downstream effector proteins. Similarly, in vivo, gefitinib and cisplatin in combination significantly inhibited tumor growth of H358^R xenografts.

Conclusion

Abnormal activation of EGFR may induce wtEGFR NSCLC cell resistance to cisplatin. The combined effects of cisplatin/gefitinib suggest that gefitinib, as a combination therapy for patients with cisplatin-resistant wtEGFR NSCLC should be considered.

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Title: Gefitinib sensitization of cisplatin-resistant wild-type EGFR non-small cell lung cancer cells
Authors: Amin Li
Weiya Cao
Xueke Liu
Yinci Zhang
Yongfang Ma
Ruyue Xu
Rongbo Zhang
Xinkuang Liu
Shuping Zhou
Ruikai Wang
Jiachang Liu
Xiaolong Tang
Publication date: 01-07-2020
Publisher: Springer Berlin Heidelberg
Keywords: NSCLC
NSCLC
Gefitinib
Published in: Journal of Cancer Research and Clinical Oncology / Issue 7/2020
Print ISSN: 0171-5216
Electronic ISSN: 1432-1335
DOI: https://doi.org/10.1007/s00432-020-03228-4

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