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

Guan,Jian; Yuan,Zhenchao; He,Juliang; Wu,Zhenjie; Liu,Bin; Lin,Xiang; Mo,Ligen; Mo,Hao

doi:10.3892/etm.2016.3713

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

Authors:
- Jian Guan
- Zhenchao Yuan
- Juliang He
- Zhenjie Wu
- Bin Liu
- Xiang Lin
- Ligen Mo
- Hao Mo
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Affiliations: Department of Bone and Soft Tissue Neurosurgery, Affiliated Tumor Hospital of Guangxi Medical University, Nanning, Guangxi 530021, P.R. China
Published online on: September 16, 2016 https://doi.org/10.3892/etm.2016.3713
Pages: 2815-2822
Copyright: © Guan et al. This is an open access article distributed under the terms of Creative Commons Attribution License.

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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.

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