Anti-tumor effects of MAGL inhibitor and its synergistic effects with SCD1 inhibitor in breast cancer

Purpose Cancer cells exhibit metabolic reprogramming to adapt to their rapid division and proliferation, including lipid metabolism. Monoacylglycerol Lipase (MAGL) is involved in the degradation of triacylglycerol. This research aims to investigate the function of MAGL in breast cancer and the underlying mechanisms. Materials and Methods Immunohistochemistry analysis was performed to estimate the expression of MAGL in breast cancer tissues. The effect of JZL184 (MAGL inhibitor) on the proliferation, apoptosis, cell cycle, migration and invasion of breast cancer was validated by CCK-8 assays, flow cytometry, scratch test, transwell invasion assay. SynergyFinder instructions was used to evaluate the synergistic effect between JZL-184 and MF-438 (SCD1 inhibitor). Western blot was employed to investigate the mechanism. Results MAGL was highly expressed in most breast cancer samples other than the corresponding normal tissues. Furthermore, JZL-184 suppressed the malignant phenotype of breast cancer by inhibiting proliferation, inducing apoptosis, blocking the cell cycle and reducing the migration and invasion ability. JZL-184 may exert the antitumor effect by down-regulating the Bcl-2/Bax and ERK-Cyclin D1 signaling pathways. In addition, the combination of JZL-184 and MF-438 illustrated a prominent synergic effect. Conclusion MAGL inhibitor significantly attenuates the malignant behavior of breast cancer, and produces a synergistic antitumor effect with SCD1 inhibitor. It provides a novel therapeutic target and antitumor strategy for breast cancer.