| Background:Gliomas are high degree of recurrence, poor prognosis of malignant brain tumor, has been a difficult problem in clinical. Many studies have shown that endocannabinoids have anti-tumor effects, including inhibition of proliferation, induction of apoptosis and inhibition of migration, but its role and mechanism on glioma has not been fully elucidated. Celastrol can inhibit proteasome activity, arrest cell cycle and induce apoptosis, which makes it a potential drug to treat glioma.Objective:Observe cell proliferation changement after regulating the endocannabinoid system with or without celastrol, explore the possible glioma therapeutic targets at the cellular level. Try to make celastrol a new drug to resist glioma.Methods:Cell growth curve was determined by cell counting method to calculate the doubling time; detecting intracellular CD133expression by Western blot; endocannabinoids, free fatty acids and ceramides were detected by LC-MS/MS method; using RT-qPCR technology to detect cannabinoid receptor CB1, CB2, cannabinoid hydrolase FAAH, MGL and other gene expression levels of mRNA with or without celastrol; using CCK-8kit to detect glioma cell proliferation after regulating endocannabinoid system with or without celastrol.Results:Doubling time, CD133, intracellular FFAs, ceramides content were significant differences. There are also significant differences between2-AG, FAAH, MGL, CB1. Celastrol inhibited glioma cells proliferation in time and dose dependent manner, up rugulated mRNA of CBRs in the process, endocannabinoids enzyme inhibitors JZL184and cannabinoid receptor agonists WIN55,212-2can enhance anti-glioma effect of celastrol. On the other hand, Celastrol can enhance the anti-tumor effect of JZL184.Conclusion:The increase in endocannabinoid levels or activating the channel signaling inhibits proliferation of glioma cells, the endocannabinoid system is an effective target for the treatment of glioma, and celastrol can be a good drug combination. |
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