Androgen Receptor(AR) and Estrogen Receptor α (ERα) Affect Cell Growth and Metastasis of Non-Small Cell Lung Cancer Through EGFR/PI3K/AKT Axis.

Abstract Background/Aims: Androgen receptor (AR), estrogen receptor α (ERα) signaling and their interaction with epidermal growth factor receptor (EGFR) signaling pathway is a potential therapeutic target in non-small cell lung cancer (NSCLC). To explore the cross communication between AR, ERα and EGFR signaling pathway, we used RNA silencing technology and sex hormones intervention in NSCLC cell line. Methods: Model system was the well-characterized A549 adenocarcinoma NSCLC cells which can express AR and ERs well. We used different concentrations of testosterone (T), estradiol (E2) intervention cells and small interfering RNA (siRNA) specifically targeting AR, ERα in A549 cells, then examined the expression of AR, ERα and EGFR/PI3K/AKT axis, followed by detection of cells proliferation, apoptosis, migration and invasion. Results: After knocked down the expression of AR, ERα, the EGFR/PI3K/AKT axis was inhibited, and the proliferation decreased, apoptosis increased, migration and invasion decreased in A549 cells. 50µM T and 50µM E2 intervention inhibited AR, ERα and EGFR/PI3K/AKT axis expression, and the proliferation decreased, apoptosis increased, migration and invasion decreased in A549 cells. 10µM T, 10µM E2 and 100µM T, 100µM E2 intervention promoted the expression of AR, ERα and EGFR/PI3K/AKT axis, which enhanced the activity and migration invasiveness of A549 cells. Conclusions: These data provide a rationale for further investigation of the antitumor activity of clinical sex hormones therapy and the development of anticancer drugs targeting sex hormone receptors in the clinic. Future .