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Overexpression of caveolin-1 reduces Taxol resistance in human osteosarcoma cells by attenuating PI3K-Akt-JNK dependent autophagy

Caveolin-1 (CAV-1), which is an oncoprotein and a tumor suppressor, is highly expressed in normal osteoblasts. Although researchers have investigated its role in human osteosarcoma, the mechanism of caveolin-1 action in osteosarcoma remains unknown. In the present study, Saos-2 and U-2 OS cells were...

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Detalles Bibliográficos
Autores principales: Guan, Jian, Yuan, Zhenchao, He, Juliang, Wu, Zhenjie, Liu, Bin, Lin, Xiang, Mo, Ligen, Mo, Hao
Formato: Online Artículo Texto
Lenguaje:English
Publicado: D.A. Spandidos 2016
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5103709/
https://www.ncbi.nlm.nih.gov/pubmed/27882079
http://dx.doi.org/10.3892/etm.2016.3713
Descripción
Sumario:Caveolin-1 (CAV-1), which is an oncoprotein and a tumor suppressor, is highly expressed in normal osteoblasts. Although researchers have investigated its role in human osteosarcoma, the mechanism of caveolin-1 action in osteosarcoma remains unknown. In the present study, Saos-2 and U-2 OS cells were cultured with a continuous induction protocol of gradually increasing Taxol concentration for 6 months to establish drug-resistant cell lines. CAV-1 expression levels in osteosarcoma cells were detected via western blotting and quantitative polymerase chain reaction. CAV-1 knockdown was achieved using a short hair-pin RNA lentivirus vector, and cell viability was analyzed by MTT assay. The effect of caveolin-1 on autophagy was investigated, and the downregulation of caveolin-1 and increased autophagy was identified in Taxol-resistant osteosarcoma cells. In addition, the results of the present study demonstrated that downregulation of caveolin-1 promotes autophagy and induces osteosarcoma cell resistance to Taxol. Notably, overexpression of CAV-1 resensitized drug-resistant cells to Taxol via declined autophagy. In conclusion, CAV-1 was demonstrated to be downregulated in Taxol-resistant osteosarcoma cells, and overexpression of CAV-1 in human osteosarcoma cells suppressed Taxol resistance by attenuating PI3K-Akt-JNK-dependent autophagy. The present findings suggest that further investigation into CAV-1's role in Taxol resistance is warranted. In the future, detection of CAV-1 may be used as an indicator to evaluate the treatment and prognosis of patients with osteosarcoma.