萝卜硫素诱导白血病细胞K562凋亡及其与化疗药协同作用的实验研究

目的:探讨萝卜硫素诱导K562白血病细胞作用及其与化疗药的协同作用。方法:琼脂半固体集落培养法和MTT法检测不同浓度的萝卜硫素对K562细胞增殖的影响;倒置显微镜观察萝卜硫素对细胞形态的影响,Annexin V-FITC/PI双标记法检测细胞凋亡情况;Western blot检测凋亡调控蛋白PARP的活性;观察萝卜硫素分别和高三尖杉酯碱、阿糖胞苷联合的抑瘤作用,用药物相互作用指数评价药物协同作用。结果:萝卜硫素能够抑制白血病K562的增殖,呈剂量依赖性;萝卜硫素引起了K562细胞形态的明显改变,显著提高了细胞的早期凋亡率,增加了促凋亡蛋白PARP的表达水平;萝卜硫素与化疗药物高三尖杉酯碱和阿糖胞苷存在明显的协同作用,其协同系数分别为0.64和0.66。结论:萝卜硫素可以诱导K562细胞发生凋亡,增加化疗药物的敏感性,具有良好的临床应用前景。

Experimental Study of Sulforaphane Effect on Cell Apoptosis of K562 and Its Synergistic Effect with Chemotherapy Drugs

Objective ：To investigate the apoptosis inducing effects of Sulforaphane （SF） in human chronic myeloid leu- kemia cell K562 and its synergistic effect with chemotherapy drugs, homoharringtonine （Horn） and cytosine arabinoside （Ara -c）. Methods：KS62 cells were firstly treated with different concentrations of SF. Then, the inhibitory effect of SF was detected by MTY and semisolid agar culture assay;morphological changes of cells were observed by inverted microscope;cell apoptosis were detected by Annexin V - FITC/PI staining. Western blot was carried out to determine the expression of ap- optosis related proteins PARP. Finally,the synergistic effects of SF with Horn and Ara - c were determined respectively. Re- sults：SF significantly inhibited the proliferation,induced cell apoptosis and morphological changes of K562 cells. Further- more,SF significantly increased the activities of pro - apoptotic proteins PARP. SF also increased sensitivity of K562 to- wards Hom and Ara - c. The combination indexes of SF with Horn and Ara - c were 0.64 and 0.66, respectively. Conclu- sions ： Our resuhs showed that SF could induce cell apoptosis of human chronic myeloid leukemia cell and increase the sensitivity to chemotherapy drugs,indicating potential clinical applications for chronic myeloid leukemia patients.