Influence of Autophagy Inhibition on Lung Adenocarcinoma Cell Migration and Invasion Ability, and Efficacy of Gefitinib

Abstract

An increasing number of studies have emphasized the role of autophagy in cancer cell metastasis and treatment of malignant tumors. Autophagy inhibitors have been widely used in combination therapies to treat advanced malignancies. Several lung adenocarcinoma cells harbor epidermal growth factor receptor (EGFR) gene mutations, and EGFR tyrosine kinase inhibitors (TKIs) are routinely used in the treatment of lung adenocarcinoma. However, a number of lung adenocarcinoma tumors do not respond or develop resistance to EGFR TKIs. The aim of the present study was to explore the effect of autophagy inhibition on the biological behavior of lung adenocarcinoma cells. In addition, whether autophagy inhibition increases the efficacy of gefitinib in lung adenocarcinoma was investigated. The activation of autophagy was inhibited via the reduction of the expression of ATG5 in A549, H1975 and HCC827 cells. ATG5 knockdown using ATG5 siRNA partially suppressed the LC3B-II expression, decreased the LC3B-I/II conversion rate and enhanced the P62 expression. Cell scratch test and Transwell assay showed that the inhibition of autophagy could impair the migration and invasion ability of cells. These studies suggested that autophagy may play a pro-survival role in lung adenocarcinoma.