耐药相关基因MDR1、MRP、LRP及其表达产物P-gp、MRP、LRP在非小细胞肺癌组织中的表达及意义

The expression and significance of the multidrug resistance-related genes MDR1、MRP、LRPmRNA and their proteins P-gp、MRP、LRP in human non-small cell lung cancer tissues

目的:研究探讨非小细胞肺癌(NSCLC)组织和癌旁组织中多药耐药基因1(multidrug resistance gene1,MDR1)、多药耐药相关蛋白(multidrug resistance-related proteins,MRP)、肺耐药蛋白(lung resistance protein,LRP)mRNA及其相应蛋白P-gp、MRP、LRP的表达情况及临床意义。方法:运用聚合酶链反应(RT-PCR)、免疫组织化学法(IHC)检测43例NSCLC组织及癌旁组织标本中耐药基因MDR1、MRP、LRPmRNA及其蛋白P-gp、MRP、LRP的表达水平。结果:MDR1、MRP和LRP mRNA3种基因在43例肿瘤组织中的表达率分别为79.06%(34/43)、65.17%(28/43)和86.05%(37/43),癌旁组织中的表达率分别为20.00%(3/15)、13.33%(2/15)和13.33%(2/15);P-gp、MRP和LRP3种耐药蛋白在肺癌组织中的表达率分别为74.42%(32/43)、67.44%(29/43)和88.37%(38/43),癌旁组织中的表达率分别为13.33%(2/15)、20.00%(3/15)和6.67%(1/15),上述3种基因及其蛋白在肺癌组织与癌旁组织的表达差异有显著性(P<0.05)。肺癌组织中既存在耐药基因MDR1、MRP和LRP的共表达,也存在耐药蛋白P-gp、MRP和LRP的共表达,3种基因与其相应蛋白表达密切相关。肺腺癌组织中MDR1及其蛋白P-gp、LRPmRNA表达率较高,与其它病理类型相比差异有显著性(P<0.05),MRPmRNA及其蛋白MRP表达与肺癌病理类型、临床分期和组织学分级无关(P>0.05)。结论:NSCLC存在着广泛的原发性多药耐药现象,耐药基因MDR1、MRP和LRPmRNA及其相应蛋白参与了肺癌多药耐药的形成,检测多药耐药基因可为指导临床用药提供一定的理论依据及策略。

Objective： To investigate the expression and significance of the multidrug resistance-related genes muhidrug resistante genel （MDR1） ,muhidrug resistance-related protein（MRP） ,lung resistance protein（LRP） mRNA and their proteins P-glycoprorein（P-gp） ,MRP,LRP in human non small cell lung cancer（NSCLC） tissues and paratumor tissues. Methods：To examine the expression level of MDR1 ,MRP,LRP mRNA and their proteins P-gp,MRP , LRP in 43 samples of NSCLC and in 15 samples of paratumor tissues by immunohistochemistry （IHC） and reverse transcription polymerase chain reaction （RT-PCR）. Results ： The expression rates of MDR1 ,MRP and LRP mRNA were 79.06% （34/43） ,65. 17% （28/43） ,86. 05% （37/43） and 20. 00% （3/15） ,13.33% （2/15）, 13. 33% （2/15）in 43 tumor tissues and in 15 paratumor tissues, respectively. The expression rates of P-gp,MRP and LRP were 74. 42% （32/43） ,67.44% （29/43） ,88. 37% （ 38/43 ） and 13. 33% （ 2/15 ） ,20. 00% （ 3/15 ） ,6. 67% （ 1/15 ） in 43 tumor tissues and in 15 paratumor tissues, respectively. There was statistic difference in the expression of MDR1 ,MRP, LRPmRNA and their tortespending proteins（P-gp,MRP,LRP） between lung cancer tissues and paratumor tissues （ P 〈 0. 05 ）. Coexpression phenomena of above-metioned three genes （ MDRI, MRP, LRP ） and their corresponding proteins （ P-gp, MRP, LRP ） was detected in the same lung cancer samples. There was close relationship between the expression of 3 genes and their corresponding proteins. The expression of MDR1 and its proten P-gp, LRP mRNA in lung adenocarcinoma was higher than that in other pathological carcinomas（ P 〈0. 05）. The expression of MRPmRNA and its corresponding protein MRP was not related to pathological type,clinical stage and classification of histodifferentiation（P 〉0.05 ）. Conclusion： Multidrug resistance is more common in NSCLC. The genes of MDR1, MRP, LRP mRNA and their corresponding proteins participated in the formation of muhidrug resistance in lung cancer. Detection of multidrug resistancerelated genes in lung cancer tissues may be useful to choice drugs.