Gastrodin Influences The Proliferation And Apoptosis Of Glioma Cells By Regulating CAMP/PKA/GRK2 Pathway

Background:Gastrodin(GAS),an organic substance obtained from the dried roots of Gastrodia elata,a member of the orchid family herbaceous plant,belongs to a group of naturally occurring phenolic compounds.Gastrodin has a good sedative and analgesic effect,as well as a hypnotic effect,especially on Neurasthenia,insomnia and headache symptoms.In recent years,some studies have found that Gastrodin has anti-tumor activity,it also plays an important role in nervous system tumors,but there is no research on the mechanism of Gastrodin in the treatment of glial tumors.Glioma--a common malignancy of the central nervous system.The higher the grade of glioma,the more malignant it is and the less likely it is to survive.This study was designed to investigate the effects of c AMP/PKA/GRK2 signaling pathway on the proliferation and apoptosis of glioma cells,the regulatory effect of Gastrodin on this signal pathway was further discussed.It provides a new idea for the treatment of glioma.MethodsAt the cellular level,U87 glial cells were treated with different concentrations of Gastrodin(2.5 ～ 80 μmol/L),and then the proliferation of glial cells was detected to determine the optimal concentration of Gastrodin.The U87 glial cells were divided into five groups,they were divided into four groups: normal control group,Gastrodin-L group(treated with 5 μmol/L GAS),Gastrodin-M group(treated with 10 μmol/L GAS),Gastrodin-L group(treated with 20 μmol/L GAS),Gastrodin + c AMP/PKA pathway inhibitor group(treated with 20 μmol/L GAS and 10 μmol/L H-89),the expression of Cyclin D 1,p21,BAX,BCL-2,Caspase-3,Camp,p-PKA,PKA,p-GRK2 and GRK2 in U87 cells were detected.ResultsThe results showed that Gastrodin at the concentration of 2.5 ～ 80 μmol/L could significantly inhibit the proliferation of U87 glial cells.In order to advance the following experiments,Gastrodin at the concentration of 5,10 and 20 μmol/L was used to stimulate U87 glial cells.Compared with the control group,Gastrodin-H group,Gastrodin-L group and Gastrodin-M group had a dose-dependent effect,and the number of apoptotic cells and cells in G 0/g 1 phase of cell cycle were significantly increased(P< 0.05),compared with Gastrodin-H group,the percentage of S phase and G 2/M phase,the number of clonal plaques,the protein levels of BCL-2 and Cyclin D 1 were significantly decreased(P < 0.05),the ratio of G 0/g 1 phase,the expression levels of Caspase-3,BAX,Camp,p-PKA,p21,p-GRK2 protein and m RNA,and the rate of apoptosis were all decreased in H-89 combined with Gastrodin group(P < 0.05),the percentage of S phase and G 2/M phase,the number of clonal plaques,the expression of BCL 2 and Cyclin D 1 protein were significantly increased(P < 0.05).ConclusioncAMP/PKA/GRK2 pathway was activated by Gastrodin,which inhibited the proliferation of glioma cells and induced apoptosis.