非霍奇金淋巴瘤多药耐药的实验研究

目的 探讨初发非霍奇金淋巴瘤(NHL)mdrl mRNA及多药耐药蛋白P糖蛋白(P-gp)、肺耐药蛋白(LRP)和多药耐药相关蛋白(MRP)的表达频率及临床意义.方法 采用逆转录多聚酶链反应(RT-PCR)半定量方法检测41例初治NHL患者淋巴结活组织中瘤细胞mdrl mRNA的表达,采用流式细胞仪免疫荧光法检测P-gP、LRP、MRP的表达,以13例反应性增生淋巴结患者作为对照组.并分析多药耐药蛋白表达与NHL临床特征的关系.结果 41例NHL患者中,11例mdrl mRNA表达阳性,8例P-gP表达阳性,7例MRP表达阳性,15例LRP表达阳性.NHL组与对照组比较,MRP阳性率差异无统计学意义(P=0.887),LRP阳性率明显增高(P=0.047).NHL患者淋巴结组织P-gP、MRP、LRP表达两两之间均不存在相关关系,P-gP表达与mdrl mRNA表达正相关(r=0.396,P=0.01).P-gP表达与临床分期、LDH水平有关(均P<0.05),而与恶性分级无关.MRP表达与临床分期、恶性分级、血清乳酸脱氢酶(LDH)水平均无关(均P>0.05),而LRP表达与三者均有关(均P<0.05).P-gP和LRP表达阳性患者的完全缓解(CR)率分别为37.5%和53.3%,低于阴性表达者(均P<0.05),化疗疗效较差,而MRP表达与化疗疗效无关.结论 P-gP、LRP可能是NHL原发耐药的主要因素,影响NHL患者的化疗疗效,而MBP与NHL原发耐药无关,不影响NHL患者的化疗疗效.

Expression and significance of P-gp/mdr1 mRNA, MRP and LRP in non-Hodgkin's lymphoma

Objective To explore the expression and clinical significance of P-glycoprotein (P-gp)/mdrl mRNA, multidrug resistance-associated protein (MRP) and lung resistance protein (LRP) in newly diagnosed non-Hodgkin's lymphoma. Methods mdrl mRNA of in 41 patients with non-Hodgkin's lymphoma was assayed by semi-quantitative RT-PCR. The expressions of P-gp, MRP and LRP proteins in lymph node viable blasts were identified by flow cytometry. The results were compared with those obtained from control cases, and the correlation of the changes with clinical outcomes was analyzed. Results (1) Among the 41 cases, the positive expression of P-gp protein was detected in 8 cases, MRP in 7 cases, LRP in 15 cases, and mdr 1 mRNA in 11 cases. (2)The P-gp and LRP levels in NHL were significantly higher than those in control group, but MRP wasn't. The P-gp over-expression was significantly associated with mdrlmRNA(r=0.396, P=0.01). No correlation was showed among the expressions of P-gp, MRP and LRP. (3) Patients with P-gp expression had a poorer outcome of chemotherapy than those with P-gp-negative (P=0.005). P-gp expression was significantly associated with higher clinical stage (P=0.046) and elevated serum lactate dehydrogenase level (P=0.032), but not associated with malignant degree (P=0.298). MRP had no impact on the outcome of chemotherapy (P=0.212), and wasn't significantly associated with higher clinical stage (P=0.369), elevated LDH (P=0.762) and higher malignant degree (P=0.451). Patients with LRP expression had a poorer outcome of chemotherapy than those LRP-negative (P=0.012). LRP expression was significantly associated with higher clinical stage (P=0.0019), elevated LDH (P=0.02) and higher malignant degree(P=0.01). Conclusion The data of this study indicate that P-gp and LRP expressions but not MRP expression are important in the mechanism of drug resistance associated with a poor clinical outcome in previously untreated NHL.