Scutellarin Increases Cisplatin-Induced Apoptosis and Autophagy to Overcome Cisplatin Resistance in Non-small Cell Lung Cancer via ERK/p53 and c-met/AKT Signaling Pathways

Scutellarin Increases Cisplatin-Induced Apoptosis and Autophagy to Overcome Cisplatin Resistance in Non-small Cell Lung Cancer via ERK/p53 and c-met/AKT Signaling Pathways

Blog Article

click here 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 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 soderhamn ottoman cover 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 resistance through apoptosis and autophagy, and suggests that combined cisplatin and scutellarin might be a novel therapeutic strategy for patients with NSCLC.