Cisplatin, as the first-line anti-tumor agent, is widely used for treatment of a variety of malignancies including non-small cell lung cancer (NSCLC).However, the acquired resistance has been a major obstacle for the clinical application.Scutellarin is a active flavone extracted from Erigeron breviscapus Hand-Mazz that has been shown to exhibit anticancer activities on various types of tumors.Here, we reported that scutellarin was capable of sensitizing A549/DDP cells to cisplatin by enhancing apoptosis and autophagy.
Mechanistic analyses indicated that cisplatin-induced caspase-3-dependent apoptosis was elevated in the presence of scutellarin through simply southern cat shirt activating extracellular signal-regulated kinases (ERK)-mediated p53 pathway.Furthermore, scutellarin also promoted cisplatin-induced cytotoxic autophagy, downregulated expression of p-AKT and c-met.Deficiency of c-met reduced p-AKT level, and inhibition of p-AKT or c-met improved autophagy in A549/DDP cells.Interestingly, loss of autophagy attenuated the synergism of this combination.
In vivo, the co-treatment of cisplatin and scutellarin notably reduced the tumor size when compared with cisplatin treatment alone.Notably, scutellarin significantly reduced the toxicity generated by cisplatin in tumor-bearing mice.This study identifies the unique role of scutellarin in reversing cisplatin here resistance through apoptosis and autophagy, and suggests that combined cisplatin and scutellarin might be a novel therapeutic strategy for patients with NSCLC.