Effects of dihydroartemisinin on the proliferation of gastric cancer cell line SGC7901 / 中华消化外科杂志

ABSTRACT

Objective To investigate the effects of dihydroartemisinin (DHA) on the proliferation of gastric cancer cell line SGC7901 and its mechanism.Methods SGC7901 cells were divided into the DHA group and the control group.SGC7901 cells in the DHA group were treated with DHA of different concentrations (6.25,12.50,25.00,50.00,100.00 μmol/L),SGC7901 cells in the control group were cultured in the 0.1％ DMSO medium.The proliferation of SGC7901 cells was detected by the MTF method at different time points (24,48,72 hours).Cell cycles of SGC7901 in the DHA group were observed by flow cytometry at 24 hours after treatment.The expressions of Cyclin A,Cyclin D1,Cyclin E,Cyclin-dependent kinase 4 (CDK4) and P16 were detected by Western blot after treating SGC7901 with DHA at concentration of 100μmol/L for 24 hours.The interaction between CDK4 with Cyclin D1 or P16 was examined using the co-immunoprecipitation assay.All data were analyzed using the one-way analysis of variance or the t test.Results The proliferation of SGC7901 cells was significantly inhibited after the treatment with DHA at different concentrations (6.25,12.50,25.00,50.00,100.00 μmol/L) for 24,48 and 72 hours (F =78.66,235.37,93.75,P ＜ 0.05).Compared with control group,the number of SCG7901 cells in the G0/G1 phase in the DHA group was significantly increased (F =18.42,P ＜0.05).After treating SGC7901 cells with DHA for 24 hours,the protein expressions of Cyclin D1 and CDK4 were 0.67 ± 0.15 and 0.64 ± 0.18 in the control group,which were significantly higher than 0.17 ± 0.05and 0.24 ± 0.06 in the DHA group (t =7.746,5.164,P ＜ 0.05).The protein expressions of Cyclin E were 0.42 ± 0.06 in the control group and 0.35 ± 0.06 in the DHA group,with no significant difference (t =2.021,P ＞ 0.05).The protein expressions of Cyclin A were 0.35 ± 0.09 in the control group and 0.38 ± 0.08 in the DHA group,with no significant difference between the 2 groups (t =1.266,P ＞ 0.05).The protein expressions of P16 were 0.29 ± 0.07 in the control group and 0.54 ± 0.12 in the DHA group,with significant difference between the 2 groups (t =4.408,P ＜ 0.05).The results of co-immunoprecipitation assay showed that DHA decreased the interaction between CDK4 and Cyclin D1,and increased the interaction between CDK4 and P16.Conclusion DHA induces SGC7901 cells arrested in G0/G1 phase,and the effect may be related with its downregulation of Cyclin D1 and CDK4,up-regulation of P16,decreasing the interaction between CDK4 and Cyclin D1,and increasing the interaction between CDK4 and P16.