title: Overexpression of caveolin-1 reduces Taxol resistance in human osteosarcoma cells by attenuating PI3K-Akt-JNK dependent autophagy.
abstract: 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.
authors.affiliation: Department of Bone and Soft Tissue Neurosurgery, Affiliated Tumor Hospital of Guangxi Medical University, Nanning, Guangxi 530021, P.R. China.
authors.forename: Jian
authors.initials: J
authors.lastname: Guan
authors.affiliation: Department of Bone and Soft Tissue Neurosurgery, Affiliated Tumor Hospital of Guangxi Medical University, Nanning, Guangxi 530021, P.R. China.
authors.forename: Zhenchao
authors.initials: Z
authors.lastname: Yuan
authors.affiliation: Department of Bone and Soft Tissue Neurosurgery, Affiliated Tumor Hospital of Guangxi Medical University, Nanning, Guangxi 530021, P.R. China.
authors.forename: Juliang
authors.initials: J
authors.lastname: He
authors.affiliation: Department of Bone and Soft Tissue Neurosurgery, Affiliated Tumor Hospital of Guangxi Medical University, Nanning, Guangxi 530021, P.R. China.
authors.forename: Zhenjie
authors.initials: Z
authors.lastname: Wu
authors.affiliation: Department of Bone and Soft Tissue Neurosurgery, Affiliated Tumor Hospital of Guangxi Medical University, Nanning, Guangxi 530021, P.R. China.
authors.forename: Bin
authors.initials: B
authors.lastname: Liu
authors.affiliation: Department of Bone and Soft Tissue Neurosurgery, Affiliated Tumor Hospital of Guangxi Medical University, Nanning, Guangxi 530021, P.R. China.
authors.forename: Xiang
authors.initials: X
authors.lastname: Lin
authors.affiliation: Department of Bone and Soft Tissue Neurosurgery, Affiliated Tumor Hospital of Guangxi Medical University, Nanning, Guangxi 530021, P.R. China.
authors.forename: Ligen
authors.initials: L
authors.lastname: Mo
authors.affiliation: Department of Bone and Soft Tissue Neurosurgery, Affiliated Tumor Hospital of Guangxi Medical University, Nanning, Guangxi 530021, P.R. China.
authors.forename: Hao
authors.initials: H
authors.lastname: Mo
keywords: Janus kinase; Taxol resistance; autophagy; caveolin-1; osteosarcoma cell