Verteporfin suppresses osteosarcoma progression by targeting the Hippo signaling pathway

摘要

Verteporfin (VP) is a specific inhibitor of yes-associated protein 1 (YAP1) that suppresses tumor progression by inhibiting YAP1 expression. The present study aimed to determine the inhibitory effect of VP on osteosarcoma and the underlying mechanism of its anticancer effects. Cell viability, cell cycle and apoptosis and cell migration and invasion were analyzed using the MTT assay, flow cytometry, wound healing assay and Trans well assay, respectively. Expressions of YAP1 and TEA domain transcription factor 1 (TEAD1) were measured using reverse transcription-quantitative PCR and western blotting, while their interaction was identified by the co-immunoprecipitation assay. In vivo mouse xenograft experiments were performed to evaluate the effect of VP on osteosarcoma growth. The results demonstrated that YAP1 and TEAD1 were highly expressed in osteosarcoma cells and tissues, whereas VP significantly downregulated the expression levels of YAP1 and TEAD1 in the osteosarcoma cell line Saos-2 compared with those in untreated control cells. In addition, compared with those in the control group, VP suppressed the viability, migration and invasion, induced cell cycle arrest in the G1 phase and promoted apoptosis in Saos-2 cells. In addition, VP inhibited mouse xenograft tumor growth in vivo compared with that observed in the control group. Notably, VP downregulated the levels of CYR61 expression in Saos-2 cells, whereas CYR61 overexpression mitigated the inhibitory effects of VP on osteosarcoma cells, as indicated by the increased viability and reduced apoptotic rates in Saos-2 cells overexpressing CYR61 compared with those in the control group. In summary, VP suppressed osteosarcoma by down-regulating the expression of YAP1 and TEAD1. Additionally, CYR61 may mediate the effects of VP on osteosarcoma progression.