RLIP76在调节小细胞肺癌多药耐药中的作用及临床意义  

Role and clinical significance of RLIP76 in regulation of multi-drug resistance of small cell lung cancer

作　　者：潘海霞[1] 白义凤[1] 胡洪林[1] 

机构地区：[1]四川省人民医院肿瘤科,成都610000

出　　处：《中华肿瘤杂志》2015年第4期266-271,共6页Chinese Journal of Oncology

基　　金：国家自然科学基金（81301910）

摘　　要：目的探讨RLIP76在调节小细胞肺癌多药耐药中的作用，并分析其表达与患者预后的关系。方法采用实时荧光定量PCR法和Western blot检测小细胞肺癌敏感细胞株H69和耐药细胞株H69AR中RLIP76的表达，应用小干扰RNA（siRNA）和eGFP—RLIP76分别转染H69AR和H69细胞，采用CCK-8法检测细胞对化疗药物的敏感性，免疫组化法检测小细胞肺癌组织中RLIP76的表达，分析RLIP76与患者预后的关系。结果H69AR和H69细胞株中RLIP76的表达水平分别为13．675±0．983和1．074±0．107，差异有统计学意义（P〈0．01）。通过siRNA下调H69AR中RLIP76的表达，能够增加细胞对化疗药物的敏感性，差异有统计学意义（P〈0．001）。通过转染eGFP—RLIP76上调H69细胞中RLIP76的表达，细胞对化疗药物的敏感性降低，差异有统计学意义（P=0．003）。124例小细胞肺癌和64例癌旁组织中RLIP76的表达率分别为61．3％和9．4％，差异有统计学意义（P〈0．01）。RLIP76的表达与患者的临床分期、对化疗的敏感性和生存时间相关（均P〈0．05）。结论RLIP76参与调节小细胞肺癌的多药耐药，可作为评估小细胞肺癌化疗敏感性和临床预后的潜在靶基因。Objective To investigate the role of RLIP76 in regulating muhi-drug resistance in small cell lung cancer （ SCLC）, and to analyze the relationship between its expression and prognosis. Methods The expressions of RLIP76 protein and gene were detected by Western blotting and real-time PCR （RT-PCR） in both the chemosensitive SCLC H69 cell line and chemoresistant H69AR cell line, respectively, siRNA was transfected into the H69AR cells to inhibit RLIP76 expression, and eGFP-RLIP76 was transfected into the H69 cells to enhance RLIP76 expression. The drug-sensitivity of cells to chemotherapeutic drugs （ADM, DDP, VP-16） were detected by CCK8 assay. The expression of RLIP76 in the SCLC tissues was detected by immunohistochemistry. The relationship of RLIP76 expression with clinicopathological features and prognosis of the patients was analyzed. Results The expression of RLIP76 in H69AR cells was 13. 675 ± 0. 983, significantly higher than 1.074±0.107 in the H69 cells （P〈0.01）. The drug-sensitivities of H69AR cells to chemotherapeutic drugs were significantly increased when the expression of RLIP76 was down-regulated （ P〈 0.001 ）. The sensitivities of H69 cells to chemotherapeutic drugs ADM, DDP and VP-16 were significantly decreased after transfection with eGFP-RLIP76 up-regulating the RLIP76 expression （ P = 0. 003 ）. The positive expression rates were 61.3% and 9.4% in the SCLC tumor tissues and para-cancerous tissues, respectively （P 〈 0. 01 ）. The expression of RLIP76 was significantly correlated with clinical stage, chemosensitivity and overall survival of the SCLC patients （P〈0.05）. Conclusions Our results suggest that RLIP76 is involved in the regulation of small cell lung cancer muhidrug resistance. RLIP76 may serve as a potential target gene to evaluate the chemosensitivity and clinical prognostic for small cell lung cancer.

关 键 词：小细胞肺癌 抗药性 肿瘤 预后 RLIP76 

分 类 号：R734.2[医药卫生—肿瘤]