Open Access

ARTICLE

The anti-oncogenic effect of 17-DMAG via the inactivation of HSP90 and MET pathway in osteosarcoma cells

by MASANORI KAWANO, KAZUHIRO TANAKA^*, ICHIRO ITONAGA, TATSUYA IWASAKI, YUTA KUBOTA, HIROSHI TSUMURA

Department of Orthopaedic Surgery, Faculty of Medicine, Oita University, Oita, 879-5593, Japan

* Corresponding Author: KAZUHIRO TANAKA. Email:

Oncology Research 2023, 31(5), 631-643. https://doi.org/10.32604/or.2023.029745

Received 06 March 2023; Accepted 18 May 2023; Issue published 21 July 2023

Abstract

Heat shock protein (HSP) 90 plays a crucial role in correcting the misfolded three-dimensional structure of proteins, assisting them in folding into proper conformations. HSP90 is critical in maintaining the normal functions of various proteins within cells, as essential factors for cellular homeostasis. Contrastingly, HSP90 simultaneously supports the maturation of cancer-related proteins, including mesenchymal epithelial transition factor (MET) within tumor cells. All osteosarcoma cell lines had elevated MET expression in the cDNA array in our possession. MET, a tyrosine kinase receptor, promotes proliferation and an anti-apoptotic state through the activation of the MET pathway constructed by HSP90. In this study, we treated osteosarcoma cells with an HSP90 inhibitor, 17-demethoxygeldanamycin hydrochloride (17-DMAG), and assessed the changes in the MET signaling pathway and also the antitumor effect of the drug. The cell cycle in osteosarcoma cells administered 17-DMAG was found to be halted at the G2/M phase. Additionally, treatment with 17-DMAG inhibited cell proliferation and induced apoptosis. Inhibition of tumor cell proliferation was also observed in an in vivo model system, mice that were treated with 17-DMAG. Based on the results of this study, we were able to confirm that 17-DMAG promotes inhibition of osteosarcoma cell proliferation and induction of apoptosis by inhibition of MET, a protein highly expressed in osteosarcoma cells. This approach may be useful for the establishment of a new treatment strategy for patients resistant to the standard treatment for osteosarcoma.

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