Abstract
NSCLC (non-small-cell lung cancer) is the deadliest cancer in the world. Artesunate is one of the most potent and rapidly acting antimalarial agents. Recently, emerging evidence has suggested the anticancer function of artesunate. In our work, we aimed to investigate the molecular mechanism of artesunate-induced growth inhibition in human lung adenocarcinoma cells and reported that the anticancer effects of artesunate is related to its ability in downregulating AKT/Survivin signaling in A549 cells. The effect of artesunate on the proliferation of A549 cells was determined by CCK-8 assay and colony formation assay; its effect on A549 cell apoptosis was evaluated by lactate dehydrogenase (LDH) release assay. The role of artesunate on the activation of AKT/Survivin signaling was analyzed by western blot and quantitative QPCR. Finally, we used two mouse tumor models to investigate the function of artesunate on the in vivo growth of lung cancer cells. Artesunate treatment caused significant growth inhibition and apoptosis in A549 cells. Mechanistically, artesunate downregulated the activation of AKT/Survivin signaling. In agreement, hyperactivation of AKT signaling restored artesunate-induced growth inhibition in A549 cells. In mouse lung cancer models, artesunate administration significantly reduced the growth of A549 cells and LLC cells in nude mice and immunocompetent mice, respectively. Our findings suggest that artesunate serves as a potential tumor suppressor in lung cancer and hopefully can provide new insight into the development of therapeutic strategies in the clinical lung cancer treatment.