Synergistic Effect of Novel EGFR Inhibitor AZD8931 and p38α siRNA in Lung Adenocarcinoma Cancer Cells

Abstract

Background:Lung cancer is the leading cause of cancer-related death with less than 5-year survival rate for both men and women worldwide. EGFR and MAPK signaling pathways have a critical role in proliferation and progression of various cancers, including lung cancer. P38 map kinase plays different role in various tissue hence showing a tissue-dependent behavior. It acts as an oncogene in some tissues while plays as tumor suppressor in some other tissues. The aim of this study was to investigate the combined effect of P38 αspecific siRNA and EGFR inhibitor on apoptosis and proliferation of A549 lung cancer cell line.Objective:This article is dedicated to the synergistic effect of novel EGFR inhibitor AZD8931 and P38 α siRNA in lung adenocarcinoma cancer cells proliferation and apoptosis.Methods and Materials:The A549 lung cancer cells were treated with P38 α- siRNA and EGFR inhibitor alone or in combination. The cytotoxic effects of P38 α- siRNA and EGFR inhibitor were determined using MTT assay. Relative P38 α and EGFR mRNA levels were measured by QRT-PCR. Induction of apoptosis were measured by FACS analysis.Results:The expression of mRNA related to P38 α, EGFR, and Her2 genes was reduced to 23.4%, 52.4%, and 75, respectively, after treatment of their inhibitors. Also, MTT assay showed that the cell viability after treatment with p38 α SiRNA, EGFR inhibitor and their combination was reduced to 51.02%, 48.9%, and 25.11%, respectively. FACS results indicated that p38 α siRNA, EGFR inhibitor and their combination, reduced the population of live cells to 49.5%, 32.2% and 14.3% in comparison to the population of untreated control cells (99.5%).Conclusion:The results of this study indicated that p38 α and EGFR might play an important role in the development and growth of lung cancer and might be a potential therapeutic target for the treatment of lung cancer.