FUBP1表达沉默对A549细胞生长和化疗敏感性影响研究  

Influence of far upstream element binding protein 1 gene silence to the proliferation and chemotherapy sensitivity of A549 cells

作　　者：黄带发[1] 曹玉华[1] 赵成民[1] 赵俊刚[2] 

机构地区：[1]沈阳军区总医院干诊科,辽宁沈阳110840 [2]中国医科大学附属盛京医院胸外科,辽宁沈阳110004

出　　处：《中华肿瘤防治杂志》2014年第5期342-345,共4页Chinese Journal of Cancer Prevention and Treatment

基　　金：辽宁省博士科研启动基金(20091108)

摘　　要：目的:探讨人远端上游元件结合蛋白1(far upstream element binding protein 1,FUBP1)基因在肺腺癌组织中的表达及其对肺腺癌A549细胞化疗敏感性的影响。方法:选取43例来源于201-03-17-2012-05-09沈阳军区总医院胸外科,手术患者的肺腺癌及相应距肿瘤>1cm的癌旁组织标本为研究对象。Real-time PCR检测FUBP1mRNA在肺腺癌组织中的表达;RNA干扰技术沉默A549细胞中FUBP1基因的表达,蛋白质印迹法检测抑制效果;MTT法和流式细胞术测定FUBP1基因表达沉默对细胞生长抑制率和凋亡率的影响。不同浓度顺铂(DDP)处理FUBP1基因表达沉默的A549细胞,检测细胞生长抑制率和凋亡率。结果:FUBP1基因在肺腺癌组织中的表达显著上调,为癌旁正常组织中FUBP1的177.65%,t=2.858,P=0.006。FUBP1随着分化程度的降低和分期的升高呈逐渐增高趋势,且与淋巴结及远处转移相关,P<0.01。siRNA-FUBP1能够显著抑制A549细胞中FUBP1蛋白的表达,F=14.726,P<0.001;而FUBP1基因表达沉默的A549细胞的生长抑制率由1.4%升高至29.5%,F=16.302,P<0.001;凋亡率由2.68%升高至5.84%,F=19.497,P<0.001。FUBP1基因表达沉默的A549细胞分别经1、3和5μg/mL DDP处理后,生长抑制率由14.418%、17.460%和23.545%分别升高至21.693%、27.513%和37.566%,相同DDP浓度的2组间比较的t值分别为21.074、25.835和29.473,P值均<0.001;DDP的IC50由(5.12±0.31)μg/mL降至(3.93±0.24)μg/mL,t=3.487,P=0.001;而凋亡率由8.85%、14.37%和18.21%分别升高至13.25%、18.46%和26.52%,相同DDP浓度组间比较的t值分别为7.279、15.878和23.111,P值均<0.001。结论:FUBP1的表达上调与肺腺癌相关,FUBP1表达沉默能够增加A549细胞的生长抑制率和凋亡率,并且可以提高A549细胞对化疗药物DDP的敏感性。OBJECTIVE：To detecte the expression of far upstream element binding protein 1 （FUBP1） gene in pul- monary adenocarcinoma tissue and the influence of FUBP1 gene to the chemotherapy sensitivity of pulmonary adenocarci- noma A549 cells. METHODS：Real-time PCR was used to detect the expression of FUBP1 gene in pulmonary adenocarci- noma tissues. The expression of FUBP1 gene in A549 cells was silenced by RNA interference, and the inhibitory effect was detected by western blot. MTT experiment and flow cytometry were used to detect the growth inhibitory rate and apopto- sis rate of the A549 cells with FUBP1 silence. After the A549 cells with FUBP1 gene silence treated with different concen- tration of DDP, the growth inhibitory rate and apoptosis rate were detected. RESULTS：The expression of FUBP1 mRNA was up-regulated obviously in pulmonary adenocarcinoma and it was 177.65% of FUBP1 in the tumor-adjacent tissues （t= 2. 858,P〈0. 001）. FUBP1 was increased along with the decreaing of differentiation and the increaing of staging, and it was related with lymph node metastasis and distance metastasis. The expression of FUBP1 protein could be inhibited with siRNA-FUBP] （F= 14. 726, P〈O. 001）. In A549 cells with FUBP1 silence, the growth inhibitory rate increased from 1.4 % to 29. 5 % （F= 16. 302,P〈0. 001）, and the apoptosis rate increased from 2. 68 %to 5.84 % （F = 19. 497, P〈0.001 ）.After the A549 cells with FUBP1 gene silence were treated with different concentration of DDP（1,3,5 μg/mL）,the growth in- hibitory rate was increased from 14. 418% ,17. 460% and 23. 545% to 21. 693% ,27. 513% and 37. 566% respectively,the t val- ues of the same concentration DDP were 21. 074,25. 835 and 29. 473 respectively,all the P were smaller than 0. 001. The apopto- sis rate increased from 8.85% ,14.37% and 18.21% to 13.25% ,18.46% and 26.52% respectively, the t values were 7. 279, 15. 878 and 23. 111 respectively, all the P were smaller than 0. 001. IC50 of DDP decreased from （5. 12 ± 0. 31） μg/mL

关 键 词：肺腺癌 远端上游元件结合蛋白1基因 化疗敏感性 A549细胞 中华肿瘤 

分 类 号：R734.2[医药卫生—肿瘤]