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World Journal of Surgical Oncology
Published in: World Journal of Surgical Oncology 1/2014

Open Access 01-12-2014 | Research

Secreted clusterin (sCLU) regulates cell proliferation and chemosensitivity to cisplatin by modulating ERK1/2 signals in human osteosarcoma cells

Authors: Hai Huang, Linna Wang, Mingyu Li, Xiaohui Wang, Lin Zhang

Published in: World Journal of Surgical Oncology | Issue 1/2014

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Abstract

Background

Several studies have shown that secreted clusterin (sCLU) up-regulation in multi-drug resistant osteosarcoma (OS) cells relates to enhanced drug resistance. Furthermore, sCLU silencing directed against sCLU induces significant reduction of cellular growth and sensitizes OS cells to chemotherapy. However, the molecular mechanisms underlying the effect of sCLU on OS cells are not known.

Methods

To evaluate the roles and possible mechanisms of sCLU in chemoresistance of OS cells to cisplatin (DPP), we utilized RNA interference to knockdown sCLU expression in the sCLU-rich U-2 OS cells and to overexpress sCLU in the sCLU-poorer KH OS cells, and further assessed the cell viability and chemosensitivity to DDP as well as possible signaling transduction pathways.

Results

The data showed that sCLU depletion inhibited growth and sensitized sCLU-rich U-2 OS cells to cisplatin in vitro and in vivo by inducing inactivation of ERK1/2, and sCLU overexpression promoted growth and increased resistance of sCLU-less KH OS cells to cisplatin in vitro and in vivo by activation of ERK1/2.

Conclusions

The data also suggests critical roles of sCLU in OS cell chemoresistance to DPP and raises the possibility of sCLU depletion as a promising approach to OS therapy.
Appendix
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Metadata
Title
Secreted clusterin (sCLU) regulates cell proliferation and chemosensitivity to cisplatin by modulating ERK1/2 signals in human osteosarcoma cells
Authors
Hai Huang
Linna Wang
Mingyu Li
Xiaohui Wang
Lin Zhang
Publication date
01-12-2014
Publisher
BioMed Central
Published in
World Journal of Surgical Oncology / Issue 1/2014
Electronic ISSN: 1477-7819
DOI
https://doi.org/10.1186/1477-7819-12-255

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