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目的探讨大黄素对K562细胞裸鼠移植瘤的生长抑制作用及其与Caspase-3和Caspase-9表达变化的关系。方法建立裸鼠K562细胞皮下移植瘤模型,随机分为大黄素低、中、高剂量(25、50、100mg/kg)3个实验组,以及模型组和羟基脲(120mg/kg)阳性对照组,每组5只,ip连续给药12d,测量各组裸鼠肿瘤体积,称取瘤体质量,计算抑瘤率。采用HE染色光镜和透射电镜观察肿瘤细胞的凋亡情况,应用RT-PCR检测肿瘤组织中caspase-3和caspase-9mRNA表达水平。Western blotting法检测肿瘤组织中proCaspase-3和proCaspase-9蛋白的表达。结果大黄素低、中、高剂量组肿瘤相对体积(RTV)分别为5.23±0.24、4.38±0.17、3.57±0.31;与模型组(10.45±0.47)相比,大黄素处理组肿瘤体积明显缩小,具有统计学意义(P<0.01)。光镜和电镜结果表明大黄素能够诱导K562细胞发生明显的凋亡。RT-PCR结果表明不同剂量的大黄素能够引起caspase-3和caspase-9mRNA的表达上调且有剂量依赖性。与模型组相比,大黄素处理组的proCaspase-3和proCaspase-9蛋白均出现明显的下调。结论大黄素能够明显抑制人K562细胞裸鼠移植瘤的生长,其机制可能与激活Caspase-3和Caspase-9信号转导通路有关。
Objective To investigate the inhibitory effect of emodin on the growth of xenografted K562 cells in nude mice and its relationship with the changes of Caspase-3 and Caspase-9 expression. Methods A subcutaneous xenograft model of K562 cells in nude mice was established and divided randomly into three experimental groups (low, middle and high doses of emodin) (25, 50 and 100 mg / kg), and the model group and the hydroxyurea (120 mg / kg) , Each group of 5, ip administration for 12 days, measuring the tumor volume of each group of nude mice, weighed tumor mass, calculated inhibition rate. The apoptosis of tumor cells was observed by HE staining and transmission electron microscopy. The expression of caspase-3 and caspase-9 mRNA in tumor tissues was detected by RT-PCR. Western blotting was used to detect the expression of proCaspase-3 and proCaspase-9 in tumor tissue. Results The relative tumor volumes (RTV) of emodin in low, medium and high dose groups were 5.23 ± 0.24, 4.38 ± 0.17 and 3.57 ± 0.31, respectively. Compared with model group (10.45 ± 0.47), tumor volume of emodin group was significantly reduced, With statistical significance (P <0.01). Light and electron microscopy results showed that emodin can induce obvious apoptosis in K562 cells. RT-PCR results showed that different doses of emodin can cause the up-regulation of caspase-3 and caspase-9 mRNAs in a dose-dependent manner. Compared with the model group, emodin treatment group proCaspase-3 and proCaspase-9 protein were significantly reduced. Conclusion Emodin can significantly inhibit the growth of human K562 cell xenografts in nude mice, and its mechanism may be related to the activation of Caspase-3 and Caspase-9 signal transduction pathway.