Tohoku J. Exp. Med., 2022 January, 256(1)

Monoacylglycerol Lipase (MAGL) Inhibition Impedes the Osteosarcoma Progression by Regulating Epithelial Mesenchymal Transition

Xiaokang Gong¹, Xin Zheng¹, Yang Huang¹, Weihai Song¹, Gang Chen¹ and Tao Chen¹

¹Department of Orthopedics, Taizhou Municipal Hospital, Taizhou, Zhejiang, China

Osteosarcoma is a primary malignancy of mesenchymal origin, and its metastasis and multidrug resistance remain major problems affecting the therapeutic effect. This study aimed to evaluate the efficacy and underlying mechanism of monoacylglycerol lipase (MAGL) on osteosarcoma progression. MAGL expression was downregulated by shMAGL or JZL184 (an MAGL inhibitor) and upregulated through plasmid. RT-PCR and Western blot were utilized to determine the expression of target molecules. CCK-8 assay, transwell assay and ROS assay were performed to investigate the inhibitory effect of MAGL on the growth and metastasis of osteosarcoma cells. The role of JZL184 on tumor growth was examined in cisplatin-resistant MG-63 (MG-63/R) xenograft model. MAGL was highly expressed in osteosarcoma cells and tissues. MAGL knockdown significantly impeded the proliferation, clone formation, invasion and migration of MG-63 cells, whereas opposite result was observed in 143B cells with MAGL overexpression. Likewise, an MAGL inhibitor JZL184 displayed reduced viability, clone formation, invasion and migration of osteosarcoma cells. Western blot of the epithelial mesenchymal transition (EMT)-related proteins indicated that MAGL knockdown or JZL184 could upregulated E-cadherin expression and downregulated vimentin expression. In vitro and in vivo experiments indicated that JZL184 re-sensitized MG-63/R cells to cisplatin. In summary, MAGL regulated osteosarcoma by modulating EMT, and JZL184 might be a promising agent for osteosarcoma patients who are resistant to cisplatin.

Keywords —— cisplatin; epithelial mesenchymal transition; JZL184; monoacylglycerol lipase; osteosarcoma

© 2022 Tohoku University Medical Press

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Tohoku J. Exp. Med 2022, 256, 19-26.

Correspondence: Tao Chen, Department of Orthopedics, Taizhou Municipal Hospital, No. 381-1 Zhongshan East Road, Jiaojiang District, Taizhou, Zhejiang 318000, China.

e-mail: chentaotz@163.com