PA-MSHA in combination with EGFR tyrosine kinase inhibitor: A new strategy to overcome the drug resistance of non-small cell lung cancer cells

6Citations
Citations of this article
9Readers
Mendeley users who have this article in their library.

Abstract

The inhibition of epidermal growth factor receptor (EGFR) signaling by Gefitinib provides a promising treatment strategy for non-small cell lung cancer (NSCLC); however, drug resistance to Gefitinib and other tyrosine kinase inhibitors presents a major issue. Using NSCLC cell lines with differential EGFR status, we examined the potency of PA-MSHA (Pseudomonas aeruginosa-mannose-sensitive hemagglutinin) in combination with Gefitinib on proliferation, apoptosis, cell cycle arrest, EGFR signaling and tumor growth. PC-9, A549, and NCI-H1975 cells were treated with PA-MSHA, Gefetinib, or PA-MSHA plus Gefetinib at different concentrations and times. The effects of the drugs on proliferation, cell cycle distribution and apoptosis were evaluated. The activation of EGFR and apoptotic signaling-related molecules was evaluated by Western blotting in the presence or absence of EGFR siRNA. Tumor growth and pathway signaling activation was assessed by xenografts in nude mice. A time-dependent and concentration-dependent cytotoxic effect of PA-MSHA was observed in all NSCLC cells tested. The combination of PA-MSHA plus Gefitinib enhanced the growth inhibition, sub-G1 content and apoptosis over that observed with either agent alone. Furthermore, the combination of PA-MSHA plus Gefitinib resulted in caspase-3/caspase-9 cleavage and increased inhibition of EGFR-dependent activation of AKT and ERK phosphorylation. Combination treatment was more effective in reducing tumor size and EGFR activation than either agent alone. These data suggest that PA-MSHA and Gefitinib function additively to suppress the proliferative effects of NSCLC cells of differential EGFR status. The combination of PA-MSHA and Gefitinib provides a potential new strategy to conquer drug resistance for anti-EGFR-targeted therapy of NSCLC.

Author supplied keywords

Cite

CITATION STYLE

APA

Zhao, X. M., Pan, S. Y., Huang, Q. L., Lu, Y. N., Wu, X. H., Chang, J. H., … Fu, X. L. (2016). PA-MSHA in combination with EGFR tyrosine kinase inhibitor: A new strategy to overcome the drug resistance of non-small cell lung cancer cells. Oncotarget, 7(31), 49384–49396. https://doi.org/10.18632/oncotarget.9891

Register to see more suggestions

Mendeley helps you to discover research relevant for your work.

Already have an account?

Save time finding and organizing research with Mendeley

Sign up for free