山东医药2017，Vol.57Issue(48)：23-27,5.DOI:10.3969/j.issn.1002-266X.2017.48.007
卡非佐米联合米托坦对人肾上腺皮质癌细胞H295R、SW13增殖及细胞周期的影响
Effects of carfilzomib combined with mitotane on proliferation and cell cycle of human adrenocortical carcinoma H295R and SW13 cells
摘要
Abstract
Objective To investigate the effects of carfilzomib combined with mitotane on the proliferation and cell cycle of human adrenocortical carcinoma (ACC) H295R and SW13 cells.Methods Human ACC H295R and SW13 cells were cultured in vitro.Using MTT to determine the IC50 values of mitotane on H295R and SW13 cells at 48 h,which were 18.42 and 62.37 μmol/L,respectively,and those of carfilzomib were 3.86 and 11.62 μmol/L.These two cell lines in the logarithmic growth phase were randomly divided into the control group,carfilzomib group,mitotane group,and the carfilzomib → mitotane group,carfilzomib + mitotane group,and the mitotane →carfilzomib group (namely according to the sequential administration).The concentrations of the two drugs were 1/8,1/4,1/2,1,2 times of IC50 values,respectively.The inhibitory rate of cell proliferation was measured at 48 h.The combine index (CI) of the two drugs was calculated according to the Chou-Talalay formula.These two cells in the logarithmic growth phase were randomly divided into the control group,mitotane monotherapy group (25 and 50 μmol/L),carfilzomib monotherapy group (1 μmol/L),carfilzomib (1 μ mol/L) → mitotane (25 and 50 μ mol/L) group.The inhibitory rate of cell proliferation at 48 h after drug intervention was detected.These two cells in the logarithmic growth phase were randomly divided into the blank group,mitotane group,carfilzomib group,carfilzomib → mitotae group,and the latter three groups were intervened at the drug concentration of IC50 for 96 h,and flow cytometry was used to detect the cell cycle.Results The proliferation inhibitory rates of H295R and SW13 cells were significantly higher in the carfilzomib→mitotane group than in the mitotane→carfilzomib group and the carfilzomib + mitotane group at the concentrations of IC50 and 2-fold IC50;the mitotane→carfilzomib group was higher than the carfilzomib + mitotane group;there were significant differences between every two groups (all P ＜ 0.05).CI value ＜ 1 was found in both the carfilzomib→mitotane group and the mitotane + carfilzomib group at the concentrations of IC50 and 2-fold IC50 in H295R and SW13 cell lines,and the CI value in the carfilzomib→mitotane group was lower than that in the mitotane + carfilzomib group (all P ＜ 0.05);CI value ＞ 1 was found in the mitotane→carfilzomib group,which was greater than that of the carfilzomib→mitotane group and the mitotane + carfilzomib group (all P ＜ 0.05).The proliferation inhibitory rates of H295 R and SW13 cells were significantly higher in the carfilzomib (1 μmol/L)→mitotane (25 and 50 μmol/L) group than in the mitotane group (25 and 50 μ mol/L),respectively.There was no significant difference in the percentage of cells in the G1,G2/M,and S phases between these four groups (P ＞ 0.05).Conclusion There are sequence-dependent antiproliferative effects of mitotane and carfilzomib on H295R and SW13 cell lines,and the sequential administration of carfilzomib followed by mitotane exhibits the strongest anticancer activity,but the combination of these two drugs has no significant effect on the cell cycle.关键词
肾上腺皮质癌/卡非佐米/米托坦/细胞增殖/细胞周期Key words
adrenocortical carcinoma/carfilzomib/mitotane/cell proliferation/cell cycle分类
医药卫生引用本文复制引用
韦庆臣,谭茹尹,杨海燕,黄振兴,梁杏欢,秦映芬,罗佐杰..卡非佐米联合米托坦对人肾上腺皮质癌细胞H295R、SW13增殖及细胞周期的影响[J].山东医药,2017,57(48):23-27,5.基金项目
国家自然科学基金资助项目(81060220). （81060220）
