FZD1基因对小细胞肺癌多药耐药作用研究  

Role of FZD1on regulating multi-drug resistance in small cell lung cancer cell

作　　者：刘换新[1,2] 张燕[1] 白义凤[2] 郭琳琅[2] 

机构地区：[1]武警广东省总队医院病理科,广东广州510507 [2]南方医科大学珠江医院病理科,广东广州510282

出　　处：《中华肿瘤防治杂志》2014年第1期5-10,共6页Chinese Journal of Cancer Prevention and Treatment

基　　金：国家自然科学基金(81172241)

摘　　要：目的:探讨FZD1在小细胞肺癌多药耐药中的作用。方法:运用QRT-PCR和蛋白质印迹法,分别从基因和蛋白水平检测小细胞肺癌敏感细胞株H69及耐药细胞株H69AR中FZD1的差异表达,同时运用QRT-PCR检测化疗敏感及耐药患者血液标本中FZD1的差异表达;采用siRNA抑制耐药细胞株H69AR中FZD1的表达,通过CCK8检测细胞对各种化疗药物(ADM,DDP,Vp-16)敏感性的变化,流式细胞仪检测细胞凋亡率的变化。结果:无论是基因水平还是蛋白水平,FZD1在H69AR细胞中的表达明显高于H69细胞,差异有统计学意义,P值分别为0.003和<0.001;FZD1在化疗耐药患者血液标本中的表达较化疗敏感者明显增高,差异有统计学意义,P<0.001。下调H69AR细胞株中FZD1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=0.020;H69AR细胞组的凋亡率为(2.037±0.49)%,较H69细胞组(9.63±0.67)%明显降低,差异有统计学意义,P=0.002。下调H69AR细胞中FZD1的表达后,H69ARSi-FZD1组细胞的凋亡率为(17.093±0.904)%,明显高于空白对照H69AR及阴性对照H69AR-NC组的(2.25±0.967)%,差异有统计学意义,P=0.007。结论:FZD1参与调节小细胞肺癌的多药耐药,下调FZD1基因的表达能够增加细胞对化疗药物的敏感性,FZD1可能通过抑制细胞凋亡而影响小细胞肺癌的多药耐药。OBJECTIVE：To investigate the role of FZD1 on regulates multi-drug resistance in small cell lung cancer. METHODS： The expression of FZD1 protein and gene were detected by Western blotting and real-time PCR （RT-PCR） in both the H69 and H69AR cell lines,respectively. Meanwhile,the differential expression of FZD1 was also detected in pe- ripheral blood samples of responders and non-responders patients. FZD1 expression was blocked by the siRNA in H69AR. The drug-sensitivities of H69AR cell lines to chemotherapy drugs such as ADM,DDP,VP-16 were detected by CCK8 as- say and apoptosis rate was detected by flow cytometry. RESULTS： Whether in the level of gene or protein levels, FZD1 was significantly increased in H69AR cells in the H69 cells （P= 0. 003;P（0. 001, respectively） ;expression was signifi- cantly higher in the H69AR cells H69 cells with a statistically significant difference. The expression of FZD1 was signifi- cantly enhanced in patients of non-responders than that in the responders （P^0. 001）. The drug-sensitivities of H69AR cells to chemotherapy drugs were increased when down-regulated the expression of the FZD1 （P：0. 020）;The apoptosis rate was significantly decreased in H69AR cell （2. 037-~0.49）~ compared with H69 cells（9.63：[：0.67）~ （P：0. 002）. The apoptosis rate was increased in H69AR-Si-FZDl（17. 093_＋0. 904）~ cells than that in H69AR and H69AR-NC group （2.25＋0. 967） % （P=0. 007）. CONCLUSIONS： Our results suggest that FZD1 is involved in the regulation of small cell lung cancer multidrug resistance and the sensitivity of cell to drug was increased by selectively silencing of the FZD1. FZD1 may affect the multidrug resistance of SCLC by decreasing cell apoptosis.

关 键 词：癌 小细胞肺 肺肿瘤 基因 FZDl 多药耐药 细胞凋亡 印迹法 蛋白质 

分 类 号：R734.2[医药卫生—肿瘤]