白花蛇舌草对大肠癌耐药移植瘤ABC转运蛋白表达的影响

Effect of Hedyotis Diffusa Willd on expression of ABC transporter in drug resistance xenograft of colorectal cancer in nude mice

目的探讨白花蛇舌草(HDW)对5-氟尿嘧啶(5-Fu)耐药大肠癌裸鼠移植瘤ABC转运蛋白表达的影响。方法构建BABL/c裸鼠人结肠癌细胞HCT-8/5-Fu的皮下移植瘤模型,按照瘤体积大小将20只移植瘤小鼠随机分成对照组和HDW干预组各10只,分别给予生理盐水0.1 m L/10 g、HDW 1 g/kg灌胃,1次/d,每周灌胃6 d,连续6周。每天观测裸鼠的生活状态;每周测量小鼠体质量和移植瘤大小2次;采用RT-PCR和HE染色方法检测移植瘤组织中ABC转运蛋白ABCC1、ABCB1、ABCG2 mRNA和MRP1、P-gp、BCRP蛋白表达情况。结果 HDW干预治疗可显著抑制移植瘤的生长。HDW干预组HCT-8/5-Fu耐药细胞移植瘤组织中ABCC1、ABCB1、ABCG2 mRNA表达量和MRP1、P-gp、BCRP蛋白表达量均明显低于对照组(P均<0.05)。结论白花蛇舌草对5-Fu耐药大肠癌裸鼠移植瘤生长有抑制作用,可明显下调移植瘤组织中ABC转运蛋白的mRNA和蛋白表达。

Objective It is to investigate the effect of Hedyotis Diffusa Willd （HDW） on ABC transporters expression in colorectal cancer xenograft of 5-fluorouracil （5-Fu） resistance in nude mouse. Methods The subcutaneous xenograft models of human colon cancer cell line HCT-8/5-Fu in BABL/c mice were constructed, and according to the tumor volume size, 20 mice were randomly divided into control group and HDW group with 10 rats in each group, and were treated with physiological sa- line 0.1 mL/10g and HDW 1 g/kg by intragastric administration respectively, 1 times/d, 6 days a week, and continuous treatment for six weeks. The daily life status of nude mice were observed; the body weight and tumor size were measured 2 times a week; the ABC, ABCB1, ABCG2, mRNA, ABCC1, MRP1, P-gp and BCRP protein expression in transplanted tumor tissues were detected by RT-PCR and HE staining. Results The growth of transplanted tumor were significantly inhibited by HDW intervention. The expression levels of ABCC1, ABCB1, ABCG2 mRNA and MRP1, P-gp, BCRP protein in HCT-8/5- Fu resistant cells in the HDW group were significantly lower than those in the control group （all P 〈 O. 05 ）. Conclusion HDW has inhibitory effect on the growth of colorectal cancer xenograft of 5-fluorouracil （5-Fu） resistance in nude mouse, it can sig- nificantly decrease the expression of mRNA and protein of ABC transporters in transplanted tumor tissues.