碘油羟基磷灰石纳米粒对兔VX2肝肿瘤多药耐药相关蛋白表达的影响

Effect of lipiodol-hydroxyapatite nanoparticle on the expression of multidrug resistance protein in rabbit VX2 hepatic tumor

目的研究碘油羟基磷灰石纳米粒(nHAP)经肝动脉灌注治疗对兔VX2肝肿瘤4种耐药蛋白-多药耐药蛋白1(multidrugresistance protein 1,MDR1)、多药耐药相关蛋白1(multidrug resistance related protein 1,MRP1)、肺耐药蛋白(lung resistance protein,LRP)、乳腺癌耐药蛋白(breast cancer resistance protein,BCRP)表达的影响。方法 100只新西兰白兔肝内肿瘤种植2周后随机分为5组,每组20只,经肝动脉灌注给药,实验设生理盐水组(A组)、nHAP组(B组)、单纯碘油组(C组)、阿霉素碘油组(D组)及碘油nHAP组(E组)。治疗2周后,免疫组组织化学和Western blotting检测4种耐药蛋白的表达。结果免疫组织化学和Westernblotting结果均提示:与A组相比,C组和D组残余肿瘤区的MDR1和BCRP表达升高,而E组则表达降低(P<0.05);LRP及MRP1表达在各组差异无统计学意义(P>0.05)。结论在常见的4种多药耐药蛋白中,MDR1和BCRP在兔VX2肝肿瘤多药耐药中可能起重要作用。单纯碘油及阿霉素碘油经肝动脉治疗可升高MDR1和BCRP的表达,而碘油nHAP可降低其表达,进而降低栓塞治疗后耐药的发生。

Objective To study the effect of lipiodol-hydroxyapatite nanoparticle on the expression of multidrug resistance protein（MDR1,MRP1,LRP and BCRP） in rabbit VX2 hepatic tumor.Methods One hundred New Zealand white rabbits with VX2 carcinoma implanted in the left lobes of hepar for two weeks were randomly divided into five groups： the physiological saline（group A）,nHAP（group B）,lipidol（group C）,ADM adding lipiodol（group D） and lipi-nHAP（group E）.Every group was infused through hepatic artery.The expressions of MDR1,MRP1,LRP and BCRP were examined by immunohistochemistry and Western blotting after two weeks treatment.Results The expressions of MDR1 and BCRP in group C and D were significantly higher than those in group A（P0.05）,expressions of the two proteins in group A were significantly higher than those in the group E（P0.05）.No difference for the expressions of LRP and MRP1 was found in five groups（P0.05）.Conclusion MDR1 and BCRP may play an important role in the multidrug-resistance of VX2 tumor among the commonly studied MDR proteins.Both the lipidol and ADM adding lipiodol can enhance the expressions of MDR1 and BCRP while the lipi-nHAP can lower the expressions so that they may reduce the happening of MDR of VX2 after the transcatheter arterial embolization（TAE）.