摘要
目的:探讨健脾解毒方对奥沙利铂抑制人结肠癌裸鼠原位移植瘤生长的增效作用及其对移植瘤铂类耐药相关铜转运蛋白ATP7A、ATP7B表达的影响,揭示健脾解毒方对奥沙利铂增效作用的部分机制。方法:建立人结肠癌裸鼠原位移植瘤模型,随机分为4组:对照组、奥沙利铂组、健脾解毒方组、健脾解毒方联合奥沙利铂组(联合用药组),治疗后观察各组移植瘤生长情况,采用实时荧光定量-PCR及免疫组化S-P法、Western-blot检测移植瘤中ATP7A、ATP7B mRNA和蛋白的表达。结果:(1)联合用药组的抑瘤率为53.6%,是单用奥沙利铂组的4.25倍;(2)奥沙利铂组裸鼠反复腹腔注射L-OHP后,移植瘤组织ATP7A和ATP7B的mRNA及蛋白表达均高于对照组(P<0.05);联合用药组移植瘤组织ATP7A和ATP7B的mRNA及蛋白表达均低于奥沙利铂组(P<0.05)。结论:健脾解毒方对奥沙利铂抑制人结肠癌裸鼠原位移植瘤生长有增效作用,其增效作用可能与下调移植瘤组织ATP7A和ATP7B的mRNA及蛋白表达,增加细胞内奥沙利铂药物的浓度有关。
Objective：To explore the synergistic effect of Jianpi Jiedu Fang（JPJDF）with the oxaliplatin on the tumor growth inhibition of orthotopic transplantation colon cancer,and investigate its effect on resistance-associated copper-transporting protein ATP7A and ATP7B induced by platinum Drugs.In order to reveal the molecular mechanisms of underlying synergistic effect of JPJDF.Methods：The orthotopic transplantation nude mice mode of human colon carcinoma were established and randomly dividied into four groups：control group,L-OHP group,JPJDF group,L-OHP combined with JPJDF group（combination group）.They were treated with different drugs respectively.We observed the growth of implanted tumor and the expression of copper-transporting protein and the mRNA expression level were measured by Flourescence quantitative PCR,immunohistochemical S-P method and Western-blot.Results：1.The tumor inhibition rate of combination group was 53.6%,4.25-fold compared to the L-OHP group.2.After repeated intraperitoneal injection of L-OHP,the ATP7A,ATP7B mRNA and protein expression were higher in L-OHP group than those in control group （P0.05）,and that of ATP7A,ATP7B were lower in combination group than those in L-OHP group （P0.05）.Conclusion：Jianpi Jiedu Fang（JPJDF）has the synergistic effect on the inhibition of the tumor growth in orthotopic transplantation nude mice of human colon carcinoma.The synergistic effect of JPJDF might be related to the down-regulation of the expression level of ATP7A,ATP7B mRNA and protein,the increase intracellular concentration of L-OHP.
出处
《辽宁中医杂志》
CAS
北大核心
2010年第5期942-946,共5页
Liaoning Journal of Traditional Chinese Medicine
基金
国家自然科学基金资助项目(30873404)
关键词
结直肠癌
健脾解毒方
奥沙利铂
铜转运蛋白
colorectal carcinoma
Jianpi Jiedu Fang
oxaliplatin
copper-transporting protein
