Evodiamine Suppresses Lung Cancer Progression Through Modulating FAK/STAT3/AKT Signaling Pathway

Lung cancer is a serious threat to human health and has become a major challenge to global public health. Evodiamine, a naturally indole alkaloid extracted from Tetradium ruticarpum (A. Juss.) T.G. Hartley, has been found to have toxic effects on various tumor cells. Nevertheless, the mechanism by which evodiamine on lung cancer remains unknown. In this study, the effects and possible mechanisms of evodiamine on lung cancer were investigated. Our data demonstrated that evodiamine suppressed the proliferation and migration of A549 and H1299 cells. Mechanistically, evodiamine operated by downregulating the phosphorylated expression of focal adhesion kinase (FAK), signal transducer and activator of transcription 3 (STAT3), and protein kinase B (AKT), while concurrently reducing the expression of CyclinA2 and CyclinB1. Notably, evodiamine inhibited the proliferation of A549 and H1299 cells by blocking the phosphorylation of FAK/STAT3/AKT induced by epidermal growth factor (EGF). Furthermore, the subcutaneous tumor models found that evodiamine slowed the growth of lung cancer in vivo. Collectively, our results showed that evodiamine inhibited the cell proliferation and migration of NSCLC and slowed subcutaneous tumor growth probably by the EGF-mediated FAK/STAT3/AKT pathway. These findings suggested that evodiamine is a promising therapeutic candidate worthy of further exploration for NSCLC treatment.