CAJ | 학술논문

目的:探讨P-gP、MRP1、BCRP等ABC转运蛋白在肝细胞癌中的表达及其与临床病理特征的关系.方法:应用RT-PCR和免疫组织化学方法检测P-gp/MDR1、MRP1、BCRP等mRNA及蛋白在34例的肝细胞癌、19例癌旁肝组织中的表达.结果:MDR1、MRP1、BCRP等mRNA在肝癌组的相对表达水平分别为1.15±0.24、0.64±0.33、1.07±0.32,在癌旁肝组织组的相对表达水平分别为0.36±0.14、0.19±0.06、0.31±0.09.MDR1、MRP1、BCRP在肝细胞癌中低分化组(Ⅲ、Ⅳ级)为1.38±0.26、0.73±0.35、1.34±0.21,在高分化组(Ⅰ、Ⅱ级)分别为0.74±0.32、0.30±0.11、0.45±0.13.P-gp、MRP1、BCRP等的阳性反应产物主要分布于细胞膜和胞浆内;在肝癌组和癌旁肝组织组的阳性表达率分别为82.35%、58.82%、79.41%和42.11%、26.32%、36.84%.P-gp、MRP1、BCRP在肝细胞癌中低分化组(Ⅲ、Ⅳ级)的阳性表达率分别为100%、81.25%、100%,在高分化组(Ⅰ、Ⅱ级)的阳性表达率分别为66.67%、38.89%、61.11%.RT-PCR及免疫组织化学均显示,P-gp、MDR1、MRP1、BCRPmRNA和蛋白在肝癌组的表达均高于癌旁肝组织组,且在低分化(Ⅲ、Ⅳ级)肝癌组织的表达高于高分化者(Ⅰ、Ⅱ级),差异有统计学意义(P<0.05).MDR1、MRP1、BCRP之间的表达无线性相关.结论:在肝细胞癌中存在原发性多药耐药现象,且多种耐药机制并存.P-gp、MDR1、MRP1、BCRP等与肝细胞癌的耐药有关,在肝癌组的表达高于癌旁肝组织组,且在肝细胞癌中的表达随着肿瘤分化程度的增高而降低,可作为肝细胞癌多药耐药性作用的靶点.
목적:탐토P-gP、MRP1、BCRP등ABC전운단백재간세포암중적표체급기여림상병리특정적관계.방법:응용RT-PCR화면역조직화학방법검측P-gp/MDR1、MRP1、BCRP등mRNA급단백재34례적간세포암、19례암방간조직중적표체.결과:MDR1、MRP1、BCRP등mRNA재간암조적상대표체수평분별위1.15±0.24、0.64±0.33、1.07±0.32,재암방간조직조적상대표체수평분별위0.36±0.14、0.19±0.06、0.31±0.09.MDR1、MRP1、BCRP재간세포암중저분화조(Ⅲ、Ⅳ급)위1.38±0.26、0.73±0.35、1.34±0.21,재고분화조(Ⅰ、Ⅱ급)분별위0.74±0.32、0.30±0.11、0.45±0.13.P-gp、MRP1、BCRP등적양성반응산물주요분포우세포막화포장내;재간암조화암방간조직조적양성표체솔분별위82.35%、58.82%、79.41%화42.11%、26.32%、36.84%.P-gp、MRP1、BCRP재간세포암중저분화조(Ⅲ、Ⅳ급)적양성표체솔분별위100%、81.25%、100%,재고분화조(Ⅰ、Ⅱ급)적양성표체솔분별위66.67%、38.89%、61.11%.RT-PCR급면역조직화학균현시,P-gp、MDR1、MRP1、BCRPmRNA화단백재간암조적표체균고우암방간조직조,차재저분화(Ⅲ、Ⅳ급)간암조직적표체고우고분화자(Ⅰ、Ⅱ급),차이유통계학의의(P<0.05).MDR1、MRP1、BCRP지간적표체무선성상관.결론:재간세포암중존재원발성다약내약현상,차다충내약궤제병존.P-gp、MDR1、MRP1、BCRP등여간세포암적내약유관,재간암조적표체고우암방간조직조,차재간세포암중적표체수착종류분화정도적증고이강저,가작위간세포암다약내약성작용적파점.
Objective: To investigate the expression of ATP-Binding Cassette Proteins including P-gp (P-glycoprotein), MRP1 (multidrug resistance associated protein 1) and BCRP (breast cancer resistance protein) in hepatocellular carcinoma and its relationship with pathological features. Methods: The expression of P-gp/MDR1 (multidrug resistance gene 1), MRP1 and BCRP in hepatocellular carcinoma was examined by RT-PCR and immunohistochemistry in 34 cases of hepatocellular carcinoma and 19 cases of paraneoplastic hepatic tissues. Results: The expression of MDR1, MRP1 and BCRP mRNA (messenger ribonucleic acid) was 1.15±0.24, 0.64±0.33, and 1.07±0.32 in hepatocellular carcinoma and 0.36±0.14, 0.19±0.06, and 0.31±0.09 in paraneoplastic hepatic tissues. The expression of MDR1, MRP1 and BCRP mRNA was 1.38±0.26, 0.73±0.35, and 1.34±0.21 in poorly differentiated hepatocellular carcinoma and 0.74±0.32, 0.30±0.11, and 0.45±0.13 in well differentiated hepatic tissues. The immunohistochemical positive substance was detected in the plasma membrane and cytoplasm. The positive rates of P-gp, MRP1 and BCRP were 82.35%, 58.82%, and 79.41% in hepatocellular carcinoma and 42.11%, 26.32%, and 36.84% in paraneoplastic hepatic tissues, respectively. The positive rates of P-gp, MRP1 and BCRP were 100.00%, 81.25%, and 100.00% in poorly differentiated hepatocellular carcinoma and 66.67%, 38.89%, and 61.11% in well differentiated hepatic tissues. The expression of three indicies in hepatocellular carcinoma was higher than that in paraneoplastic hepatic tissues (P<0.05). The expression of P-gp/MDR1, MRP1 and BCRP in poorly differentiated hepatocellular carcinoma was higher than that in well differentiated hepatic tissues (P<0.05). No correlation was found among the three indices. Conclusion: Intrinsic multidrug resistance exsists in hepatocellular carcinoma, with various mechanisms. The multidrug resistance of HCC (hepatic cell carcinoma) is related to P-gp/MDR1, MRP1 and BCRP. MRP1 and BCRP may be targets for reversing multidrug resistance.