Molecular Mechanism Of Glycyrrhetinic Acid Inhibits Invasion And Migration Of Prostate Cancer Cells

BLM helicase is a key member of the RecQ helicase families and involved in replication,transcription,repair and maintenance of telomere metabolism in DNA,plays an important role in maintaining the stability of chromosome.The lack of the BLM helicase will lead to the Bloom syndrome as well as a genetic instability in patients with various types of cancer such as prostate cancer,lung cancer,leukemia and so on.Glycyrrhetinic acid formed by the hydrolysis of glycyrrhizic acid as a compound with five rings three terpenes.In recent years,researches revealed that glycyrrhetinic acid inhibited the growing of the liver cancer,lung cancer,cervical cancer,gastric cancer and made less toxic to normal cells.There are also research reports that glycyrrhetinic acid can bind the BLM helicase for inhibiting activity of BLM helicase.However,there is no report on the effects of glycyrrhetinic acid combined with BLM helicase on the growth of prostate cancer PC3 cells.Research methods are as follows:Cell proliferation,invasion,migration and apoptosis had been monitored by MTT assay,Transwell,scratch and flow cytometry respectively.The transcription levels of Caspase-3 and BLM gene were tested by real-time quantitative PCR detection of the BLM as well as their expression levels of protein were detected by western-blot.In order to study the expression of the BLM helicase and explore the mechanism of the cell proliferation,migration invasion and apoptosis after the treatment of prostate cancer PC3 cells with glycyrrhetinic acid.The results are as follows:1.MTT results revealed that the effect on cell proliferation was not significant(P>0.05)when the concentration of glycyrrhetic acid under 0.12 mol/L.The proliferation of cell was gradually decreased with the increase of drug concentration when the concentration of glycyrrhetic acid is greater than 0.12 mol/L.2.The results on invasion and migration ability of the cells showed that their levels decreased obviously(P<0.01)when the concentration of glycyrrhetinic acid was above 0.10mol/L.3.Flow cytometry screening results showed that the control group the apoptosis rate was33.21% ± 1.07 and the apoptosis rate were 45.25% ± 2.05 and 43.85% ± 2.02 when glycyrrhetinic acid concentration was 0.10 mol/L and 0.15 mol/L.They have significant difference(P<0.01).4.Fluorescence quantitative PCR results showed that the expression of BLM gene decreased significantly and the expression of Caspase-3 gene increased significantly in PC3 cells compared with the control group when the concentration of glycyrrhetinic acid was above 0.12 mol/L.5.Western-blot results showed that BLM helicase protein expression was significantly reduced while the expression of Caspase-3 protein was significantly increased when the concentration of glycyrrhetinic acid in 0.12 mol/L.