中国临床药理学杂志2025，Vol.41Issue(16)：2293-2298,6.DOI:10.13699/j.cnki.1001-6821.2025.16.008
大黄素抑制人白血病K562/阿霉素耐药细胞化疗耐药作用的研究
Research of inhibitory effect of emodin on chemotherapy resistance in human leukemia K562/adriamycin-resistant cells
摘要
Abstract
Objective To investigate the effect of emodin(Emo)on chemotherapy resistance of human leukemia K562/adriamycin-resistant(K562/ADR)cells and its mechanism.Methods K562/ADR cells were assigned to control group and experimental-L,-M,-H groups.Experimental-L,-M,-H groups were incubated with Emo at concentrations of 5,10,and 20 μmnol·L-1,respectively.Control group was treated with 0.1％dimethyl sulfoxide.Methyl thiazolyl tetrazolium(MTT)assay was used to detect the effect of Emo on chemotherapy resistance in K562/ADR cells.Fluorescence analysis was used to detect the intracellular accumulation of adriamycin.Flow cytometry was used to detect the cell cycle and apoptosis.Polymerase chain reaction was used to detect the mRNA expression level of P-glycoprotein(P-gp).In addition,Western blot was used to detect the protein expression level of P-gp and nuclear factor-kappa B(NF-κB)pathway related proteins.Results The half maximal inhibitory concentrations(IC50)of K562/ADR cells to adriamycin in experimental-M,-H groups and control group were(20.91±2.03),(11.79±0.89)and(38.00±2.61)μg·ml-1;the intracellular adriamycin-associated mean fluorescence intensities(× 104)were(5.22±0.66),(7.47±0.77)and(2.69±0.69);the proportions of G0/G1 phase cells were(37.81±3.47)％,(28.05±2.86)％and(51.18±5.06)％;the proportions of S phase cells were(19.89±2.98)％,(15.24±2.21)％and(32.15±3.20)％;the proportions of G2/M phase cells were(40.65±3.33)％,(55.75±4.55)％and(13.63±2.29)％;the cell apoptosis rates at 48 hours were(39.91±3.51)％,(46.26±4.06)％and(21.45±1.92)％;the relative expression levels of P-gp mRNA were 68.10±9.61,31.01±8.90 and 100.00±12.22;the relative expression levels of P-gp protein were 77.01±8.31,63.65±7.72 and 100.00±7.07;the relative expression levels of p65(RelA/p65)in nucleus were 126.10±8.17,157.58±11.87 and 100.00±8.55;the relative expression levels of phosphorylated-inhibitor of nuclear factor κB protein α(p-IκBα)in cytoplasm were 132.45±13.46,150.97±9.47 and 100.00±7.35;the relative expression levels of IκBαin cytoplasm were 82.10±5.95,73.20±6.39 and 100.00±5.84;the relative expression levels of phosphorylated-inhibitor of kappa B kinase α/β(p-IKKα/β)in cytoplasm were 126.23±6.63,120.61±7.70 and 100.00±7.96,respectively.Compared the above indexes of the experimental-M and experimental-H groups with those of the control group,and the differences were statistically significant(P＜0.05,P＜0.01,P＜0.001).Conclusion Emo can inhibit adriamycin chemotherapy resistance in K562/ADR cells by activating the NF-κB pathway and subsequently down-regulating the expression of P-gp.关键词
大黄素/K562/阿霉素耐药细胞/核因子-κB/化疗耐药/P-糖蛋白Key words
emodin/K562/adriamycin-resistant cells/nuclear factor-kappa B/chemotherapy resistance/P-glycoprotein分类
医药卫生引用本文复制引用
江洁,郭文雅,刘静萱,高霄飞,张小丽,姚丽华,黎玉华..大黄素抑制人白血病K562/阿霉素耐药细胞化疗耐药作用的研究[J].中国临床药理学杂志,2025,41(16):2293-2298,6.基金项目
国家自然科学基金青年科学基金资助项目(82104285) （82104285）
江西省中医药科技计划基金资助项目(2023B1382) （2023B1382）
江西省卫生健康委科技计划基金资助项目(202140141) （202140141）
