The loss of endothelin-2 exhibits an anticancer effect in A549 human lung adenocarcinoma cell line

Abstract

Lung cancer is the leading cause of cancer-related deaths worldwide, and adenocarcinoma is the most common subtype of lung cancer. Endothelin-2 (ET-2) is expressed in the epithelium of alveoli, and its expression is increased in cancer. However, the role of ET-2 in lung adenocarcinoma remains unclear. This study aimed to investigate the pathophysiological functions of ET-2 in A549 human lung adenocarcinoma cells. We analyzed the expression of ET-2 mRNA in lung adenocarcinoma tissues compared with that in nontumor lung tissues using public online databases. The function of ET-2 in A549 cells was investigated using siRNA. ET-2 mRNA level was upregulated in lung adenocarcinoma tissues, and high ET-2 level was associated with poor overall survival in patients with lung adenocarcinoma. ET-2 silencing reduced the proliferation, migration, and invasion, and enhanced apoptosis in A549 cells. Mechanistically, ET-2 silencing reduced the expression levels of X-linked inhibitor of apoptosis and survivin, which are members of the inhibitor apoptosis protein family. In addition, silencing ET-2 inhibited epithelial–mesenchymal transition, which halted migration. Therefore, the specific targeting of ET-2 may be a potential treatment strategy for lung adenocarcinoma.