浙贝黄芩汤调控wip1-p53抑制kasumi-1荷瘤小鼠皮下移植瘤增殖机制研究

Mechanism of Zhebei Huangqin Decoction for inhibiting proliferation of kasumi-1 tumor-bearing mice by regulating wip1-p53

目的应用浙贝黄芩汤对NOD/SCID皮下荷瘤小鼠进行干预,探讨其抗白血病作用机制。方法 20只NOD/SCID小鼠皮下注射人白血病细胞kasumi-1构建移植瘤模型,随机分为模型组、化疗组、中药组及联合组,分别以蒸馏水、柔红霉素+阿糖胞苷、浙贝黄芩汤及中西药联合干预荷瘤小鼠。观测各组小鼠生存状态、体质量、移植瘤体积及重量、血常规变化,RT-PCR检测移植瘤细胞wip1 mRNA及p53 mRNA表达水平。结果各组小鼠皮下移植瘤体积均逐渐增长,其中联合组肿瘤体积及重量最小(P<0.05);联合组血小板计数较荷瘤前下降(P>0.05),其余3组血小板计数较荷瘤前均明显增高(P<0.05);与模型组比较,中药组移植瘤细胞wip1 mRNA表达下调,p53 mRNA表达明显上调(P<0.01),化疗组反之,联合组与模型组持平。结论浙贝黄芩汤通过降低wip1表达、促进p53转录调节功能恢复,抑制白血病细胞增殖,部分逆转耐药。

Objective To investigate the anti-leukemia mechanism of Zhebei Huangqin Decoction in NOD/SCID subcutaneous tumor-bearing mice.Methods Twenty NOD/SCID mice were injected subcutaneously with kasumi-1 cell, then divided randomly into model group, chemotherapy group, CSFD group and DA+CSFD group.The tumor-bearing mice were intervened by distilled water, daunorubicin+cytarabine, Zhebei Huangqin Decoction and Chinese and Western medicine.The living state, body weight, transplanted tumor volume and weight, and blood routine changes of mice in each group were observed.The expression levels of wip1 mRNA and p53 mRNA in transplanted tumor cells were detected by RT-PCR.The expression level of wiP1 and p53 were detected by real-time PCR.Results The volume of subcutaneous transplanted tumor in each group increased gradually, of them the DA+CSFD group had the smallest tumor volume and weight(P<0.05);the platelets in DA+CSFD group were lower than before(P>0.05),and that in the other three groups were significantly higher than before(P<0.05);compared with the model group, the expression of wip1 mRNA in the CSFD group was decreased, and the expression of p53 mRNA in the CSFD group was significantly up-regulated(P<0.01),that in the DA group was down-regulated and that in the DA+CSFD group was the same as the model group.Conclusion CSFD could reduce the expression of wip1,and promote the recovery of p53 transcription regulation function, inhibit the proliferation of leukemia cells and reverse part of drug resistance.