Abstract:

Abstract:Objective To investigate the influence of oridonin combined with melphalan in cell proliferation,apoptosis and cell cycle of myeloma RPMI8226 cells and their synergistic effect,and to clarify the cytotoxin enhanced effect of the combination of the two drugs on myeloma cells. Methods The RPMI-8226 cells were divided into blank  control group,oridonin（10  μmol/L）　group,melphalan（30  μmol/L）group and oridonin(10 μmol/L) + melphalan(30 μmol/L) group.The inhibitory rates of proliferation of RPMI-8226 cells were detected by MTT assay after treated with oridonin,melphalan alone or in  combination  at different time.The drug synergistic effect was expressed by coefficient of drug interaction (CDI).The change of cell cycle was analyzed by flow cytometry,and the apoptotic rate was detected by Annexin-Ⅴ/PI staining.Results Compared with blank control group,the inhibitory rates of proliferation of RPMI-8226 in oridonin,melphalan and oridonin+melphalan group were significantly increased(P<0.01) in a time-dependent manner.Compared with single drug groups,the inhibitory rates in oridonin+melphalan group at different time were significantly increased (P<0.01).The CDI values of two drugs at different time were less than 1,which indicated that oridonin could improve the cytotoxicity of melphalan.The apoptotic rate of combination use of two drugs was 43.06%±1.96％,which was significantly higher than single oridonin (15.01%±0.47％) and melphalan (20.03%±1.30％) (P<0.01).Flow cytometry DNA analysis showed that oridonin,melphalan or combination use could induce the arrest of most RPMI-8226 cells at G0/G1 phase,the ratio of RPMI-8226 cells at  S phase was reduced,there was significant difference between drug groups and blank control group (P<0.01),and there also was significant difference between oridonin+melphalan  group and  single drug  groups (P<0.01).Conclusion Oridonin combined with melphalan can synergisticly inhibit the proliferation of RPMI-8226 myeloma cells by arresting cell cycle and inducing apoptosis.

Key words: myeloma cells；oridonin；melphalan；apoptosis；cell cycle; , synergistic effect