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Updated: Oct 23, 2025

Intratibial Osteosarcoma Cell Injection to Generate Orthotopic Osteosarcoma and Lung Metastasis Mouse Models
Published on: October 28, 2021
Verteporfin suppresses osteosarcoma progression by targeting the Hippo signaling pathway
Xianliang Yang1,2, Youjia Xu1, Chao Jiang2
1Department of Orthopedics, The Second Affiliated Hospital of Soochow University, Suzhou, Jiangsu 215004, P.R. China.
Abstract:
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 Transwell 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 downregulating the expression of YAP1 and TEAD1. Additionally, CYR61 may mediate the effects of VP on osteosarcoma progression.
Insights
Verteporfin (VP) effectively inhibits osteosarcoma progression by downregulating YAP1 and TEAD1 expression. This targeted approach suppresses tumor cell viability, migration, and invasion, offering a promising therapeutic strategy for osteosarcoma.
Area of Science:
- Oncology
- Molecular Biology
- Biochemistry
Background:
- Osteosarcoma is a primary bone malignancy with limited effective treatments.
- Yes-associated protein 1 (YAP1) and TEA domain transcription factor 1 (TEAD1) are implicated in tumor progression.
- Verteporfin (VP) is a known inhibitor of YAP1 signaling.
Purpose of the Study:
- To investigate the inhibitory effects of Verteporfin (VP) on osteosarcoma.
- To elucidate the underlying molecular mechanisms of VP's anticancer activity in osteosarcoma.
- To evaluate the therapeutic potential of VP against osteosarcoma progression.
Main Methods:
- Cell viability, cell cycle, apoptosis, migration, and invasion assays were performed.
- Gene and protein expression levels of YAP1, TEAD1, and CYR61 were analyzed.
- Co-immunoprecipitation identified YAP1 and TEAD1 interactions.
- In vivo mouse xenograft models assessed tumor growth inhibition.
Main Results:
- YAP1 and TEAD1 were highly expressed in osteosarcoma.
- VP significantly downregulated YAP1 and TEAD1 expression in Saos-2 cells.
- VP suppressed osteosarcoma cell viability, migration, invasion, and induced apoptosis and G1 cell cycle arrest.
- VP inhibited tumor growth in a mouse xenograft model.
- CYR61 overexpression partially reversed VP's inhibitory effects.
Conclusions:
- Verteporfin (VP) effectively suppresses osteosarcoma progression by inhibiting YAP1 and TEAD1 expression.
- VP demonstrates significant anticancer effects on osteosarcoma cells in vitro and in vivo.
- CYR61 may play a mediating role in VP's therapeutic action against osteosarcoma.
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