复方浙贝颗粒联合顺铂对急性淋巴细胞白血病耐药细胞株移植瘤细胞耐药相关酶表达的影响

Effects on Expression of Drug-resistant Enzymes in Transplanted Tumor Cells of Acute Lymphoblastic Leukemia Cell Line Treated by Compound Zhebei Granules Combined with Cisplatin

目的观察复方浙贝颗粒联合顺铂(CDDP)对急性淋巴细胞白血病耐药细胞株(L1210/CDDP)移植瘤细胞耐药相关酶表达的影响,探讨其抗急性淋巴细胞白血病的作用机制。方法将急性淋巴细胞白血病多药耐药细胞株L1210/CDDP细胞接种于DBA/2小鼠腋前皮下构建多药耐药移植瘤模型,成模后按随机数字表法将移植瘤小鼠分为模型组、CDDP组、高剂量复方浙贝颗粒联合CDDP组、中剂量复方浙贝颗粒联合CDDP组、低剂量复方浙贝颗粒联合CDDP组、中剂量复方浙贝颗粒组,分组当日开始给药,隔日1次,共14d;实验结束后处死小鼠,剥离肿瘤,将瘤块组织制成切片,免疫组化检测L1210/CDDP移植瘤细胞耐药相关酶谷胱甘肽S转移酶(GST)、拓扑异构酶Ⅱ(TopⅡ)的表达。结果与模型组和CDDP组比较,各剂量复方浙贝颗粒联合CDDP组均能提高L1210/CDDP移植瘤的抑制率(P<0.05);各组生存期比较,高剂量复方浙贝颗粒联合CDDP组最优,平均53.7d(P<0.05),最长74d;与模型组比较,CDDP组和中、高剂量复方浙贝颗粒联合CDDP组GST表达均明显降低(P<0.05),CDDP组、中剂量复方浙贝颗粒组和各剂量复方浙贝颗粒联合CDDP组TopⅡ表达均明显升高(P<0.05);与CDDP组比较,中、高剂量复方浙贝颗粒联合CDDP组GST表达明显降低(P<0.05,P<0.01),复方浙贝颗粒高剂量联合CDDP组TopⅡ表达明显升高(P<0.05)。结论复方浙贝颗粒联合顺铂能提高L1210/CDDP移植瘤的肿瘤抑制率,其机制可能是通过调节肿瘤多药耐药相关酶GST/TopⅡ通路逆转多药耐药性,从而增加肿瘤细胞对药物的敏感性。

Objective To explore the anti-tumor effects of Compound Zhebei Granules combined with cisplatin(CDDP)on mice with acute lymphoblastic leukemia cell line(L1210/CDDP),and the expression of drug-resistant enzymes;To explore its mechanism of action against acute lymphoblastic leukemia.Methods Multidrug-resistant transplanted tumor model was established by inoculating acute lymphoblastic leukemia multidrug-resistant cell line L1210 CDDP subcutaneously in DBA/2 mice.The transplanted tumor mice were divided into model group,CDDP group,Compound Zhebei Granules high-dose combined with CDDP group,medium-dose combined with CDDP group,low-dose combined with CDDP group,and medium-dose Compound Zhebei Granules groups according to random number table method.Each group was given medication since the group were divided,every other day,for 14 d.The mice were sacrificed after the experiment,and the tumors were dissected into sections.The expression of drug resistance-related enzymes GST and TopⅡin transplanted L1210 CDDP cell line was detected by immunohistochemistry.Results Compared with model group and CDDP group,Compound Zhebei Granules combined with CDDP groups could increase the inhibition rate of transplanted L1210 CDDP cell line(P<0.05).The survival time of Compound Zhebei Granules high-dose combined with CDDP group was the best(P<0.05),with an average of 53.7 days and a maximum of 74 days.Compared with model group,GST of CDDP group and Compound Zhebei Granules high-dose combined with CDDP group,medium-dose combined with CDDP group decreased significantly(P<0.05);TopⅡin CDDP group and medium-dose Compound Zhebei Granules and other Compound Zhebei Granules combined with CDDP groups increased significantly(P<0.05).Compared with CDDP group,the expression of GST in Compound Zhebei Granules high-dose and medium-dose group combined with CDDP group decreased significantly(P<0.05,P<0.01),the expression of TopⅡin Compound Zhebei Granules high-dose combined with CDDP group increased significantly(P<0.05).Conclusion Compound Zhebei Granules combined with CDDP can improve the tumor inhibition rate of transplanted acute lymphoblastic leukemia drug-resistant cell lines.Its mechanism is to reverse multidrug resistance by regulating the GST/TopⅡpathway of multidrug resistance-related enzymes,thereby increasing the sensitivity of cancer cells to drugs.