The Anticancer Effect Of Verteporfin On Head And Neck Squamous Carcinoma Cells And Its Mechanism

Head and Neck Cancer(HNC)is the sixth most common malignant tumor in the world.More than 90% of the pathological types are Head and Neck Squamous Cell Carcinoma(HNSCC).Studies indicate that the occurrence of HNC is related to tobacco use,alcohol consumption and high risk Human papillomavirus(HPV)infection.Because lack of effective early detection and risk assessment,more than 50% of HNC patients are diagnosed in advanced stages.Despite the development of standard therapies,including surgery,radiotherapy and chemotherapy,survival rates for HNC patients have not changed significantly over the past three decades.The Hippo pathway plays an important role in regulating tissue growth and organ size.Yes-associated protein(YAP)is a key effector of the Hippo pathway.Aberrant activation of YAP has emerged as an important driver for tumorigenesis,chemoresistance and metastasis.Our results showed that YAP1 expression was significantly upregulated in HNC tissues compared with tumor-adjacent normal tissues.Verteporfin(VP)is a photosensitizer approved by the US Food and Drug Administration for photodynamic therapy in patients with age-related macular degeneration,which effectively inhibits the transcriptional activity of YAP1.Current studies have shown that VP has an anticancer effect on a variety of solid tumors.However,the effects of VP on head and neck squamous cell carcinoma have seldom been reported.In this study,we systematically studied the anticancer activity and potential mechanism of VP on HPV-16 positive and negative HNSCC cells.The cell proliferation assay show that the inhibitory effects of VP on HNSCC cells were markedly enhanced by light activation compared with without light activation.VP significantly inhibited HNSCC cell clone formation,migration and invasion,induced apoptosis,and arrested the cell cycle at the S/G2 phase.The anticancer effect of VP on HNSCC was confirmed by the inhibition of xenograft growth in vivo.VP significantly attenuated the expression of genes related to epithelial-mesenchymal transition(YAP1,Snail,CTNNB1 and EGFR)and stemness(Oct4 and YAP1)and increased E-cadherin expression in HNSCC cells.In addition,VP significantly inhibited PD-L1 expression in HNSCC cells.Our results indicate that YAP1 overexpression is involved in HNSCC tumorigenesis and verteporfin is a potential therapeutic drug for HNSCC.