Abstract
AimsApproximately 20% of head and neck squamous cell carcinomas (HNSCCs) are caused by human papillomavirus (HPV) infection. The effect of arsenic trioxide (ATO) on HPV oncogene expression of HNSCC cells remains unknown. In this study, we investigated the anti-cancer activity and possible molecular pathways of ATO on the six HNSCC cell lines (three HPV-positive and three HPV-negative). MethodsThe effects of ATO on the cell proliferation, apoptosis, cell cycle of HNSCC cells were analyzed using CCK-8 assay, colony formation and flow cytometry. Transwell assay was used to examine the effect of ATO on cell migration. The transcriptional and protein expression of key genes were determined by real-time PCR and Western blot, respectively. Using a xenograft model, we assessed the effects of ATO on HNSCC cells in vivo. Key findingsHPV-positive and -negative HNSCC cells had different expression of key genes. ATO inhibited HNSCC cell proliferation and migration and induced apoptosis and these effects were more significant in HPV-positive HNSCC cells than in HPV-negative HNSCC cells. ATO treatment reduced the expression of HPV16-E6/E7 and cyclin D1 proteins and enhanced the expression of p16, pRb, and p53 in HPV-positive HNSCC cells. By contrast, ATO treatment reduced the expression of epidermal growth factor receptor, cyclin D1 and mutant p53 and enhanced the expression of pRb in HPV-negative HNSCC cells. Anti-cancer effect of ATO on HNSCCs was confirmed by inhibiting xenograft growth in vivo. SignificanceOur data suggest that ATO is a potential therapeutic drug for HNSCCs, especially HPV-positive HNSCCs.
Published Version
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