Abstract
The combination of radiotherapy and chemotherapy has significantly improved survival rates for patients with nasopharyngeal carcinoma (NPC). Nonetheless, some patients still experience poor outcomes, potentially due to resistance to cisplatin, a widely used chemotherapeutic agent. Scutellarein, a compound extracted from Scutellaria baicalensis, has anticancer properties. In the present study it was examined whether scutellarein could enhance the anticancer effects of cisplatin in NPC cells. The NPC cell line, NPC/HK1, was used in the present study. Morphological assessment, MTT, ELISA, and immunoblotting assays were performed to evaluate cell membrane blebbing, viability, cytokeratin 18 fragment release, and the expression of autophagy and apoptosis markers, respectively. The results demonstrated that the combination of scutellarein and cisplatin increased cell viability inhibition, the number of membrane blebbing cells, the expression of apoptosis markers (cleaved caspase-8, cleaved caspase-7, and cleaved PARP), and the cytokeratin 18 fragment levels compared with treatments with scutellarein or cisplatin alone. Scutellarein also decreased the expression of Beclin 1 and autophagy related 3, which are markers of autophagy triggered by cisplatin. Treatment with the autophagy inhibitor, 3-methyladenine, did not enhance cisplatin-induced viability inhibition and cytokeratin 18 fragment release. Additionally, scutellarein inhibited cisplatin-induced AKT phosphorylation and multidrug resistance protein 1 (MDR1) expression, a protein linked to drug resistance. AKT phosphorylation and MDR1 expression triggered by cisplatin were inhibited by treatment with LY294002, a PI3K/AKT inhibitor. Moreover, treatment with the MDR1 inhibitor, PSC833, inhibited MDR1 expression and increased the cisplatin-induced viability inhibition and cytokeratin 18 fragment release. These findings indicated that scutellarein enhances the anticancer effects of cisplatin by inhibiting the PI3K/AKT-MDR1 signaling pathway in NPC/HK1 cells.