The Relation Of Gambogic Acid's Anti-proliferation Effect And HERG Expression In Multiple Myeloma

Objective: To investigate the effect of gambogic acid on cell proliferation and apoptosis in the multiple myeloma RPMI8226 cell line, and the regulation of HERG potassium channels by gambogic acid.Methods: The effect of gambogic acid on the growth of RPMI8266 was studied by 3-(4,5- Dimethyl-2-thiazolyl)-2,5-diphenyl-2H-tetrazolium(MTT)assay; Apoptosis was detected by flow cytometry(FCM); The expressions of HERG potassium channels at mRNA level were detected by RT-PCR; Western blot was applied to assess the expression of HERG protein.Results:①The gambogic acid dose-and time-dependently inhibited RPMI8226 cells proliferation. The IC50 for 24 h was 0.32±0.03μmol/L. The gambogic acid can induce cell apoptosis. With the concentration of gambogic acid increased, the apoptosis rate also increases accordingly in a dose-dependently manner. When the concentration of gambogic acid is 0.2μmol/L, the apoptosis rate could reach 54.00±0.75%. Compared with control, the P value was statistically significant(P<0.01).②The mRNA and protein expression of HERG potassium channels were down regulated by E-4031 and dose dependently by gambogic acid. Comparison of experimental and control groups electrophoresis band intensity ratio, the P value was statistically significant(P<0.05).③The effect was more predominance by alliance use of gambogic acid and E-4031, Compare with control groups electrophoresis band intensity ratio, the P value was statistically significant(P<0.05), and the inhibition effect of cell proliferation was also predominance.Conclusion: Gambogic acid could obviously inhibit the proliferation and induce apo- ptosis in RPMI8266 cell line in vitro,which might be related to the down regulation of HERG potassium channels protein and gene. If gambogic acid and E4031 are used to- gether,the effect of inhibiting tumor cells could increase.