CYLD抑制自噬提高膀胱癌细胞吉西他滨化疗敏感性  

CYLD improves bladder cancer gemcitabine chemosensitivity via suppressing autophagy

作　　者：殷雷[1] 殷睿[2] 李文佳[3] 刘帅[1] 吕家驹[1] 

机构地区：[1]山东大学附属省立医院泌尿外科,山东济南250021 [2]山东大学附属生殖医院医务科,山东济南250001 [3]山东大学附属省立医院心内科,山东济南250021

出　　处：《山东大学学报（医学版）》2017年第8期1-6,共6页Journal of Shandong University:Health Sciences

基　　金：山东省自然科学基金面上项目(2014ZRB14081);山东省自然科学基金(2014ZRB14513);山东省重点研发计划(2015GSF118055);山东省医药卫生科技发展计划(2014WS0341)

摘　　要：目的探讨肿瘤抑制因子CYLD提高膀胱癌细胞吉西他滨化疗敏感性。方法构建CYLD过表达质粒转染的人膀胱癌细胞株T24、253J,将细胞分为仅加入脂质体的对照组,转染空载质粒的空载组和CYLD组。Transw ell实验检测CYLD对膀胱癌细胞迁移/侵袭能力的影响,CCK8法检测膀胱癌细胞对吉西他滨的化疗敏感性,Western blotting、吖啶橙染色、电镜等检测自噬蛋白表达水平。结果与对照组和空载组相比,CYLD组通过Transw ell小室的细胞数目明显减少(P<0.05),24 h半抑制浓度(IC50)明显降低(P<0.05),自噬相关蛋白LC3、Beclin 1表达降低,p62表达增高,吖啶橙染色及电镜观察发现自噬溶酶体及自噬泡减少。结论肿瘤抑制因子CYLD可以抑制膀胱癌细胞的迁移/侵袭能力,并通过抑制自噬提高膀胱癌细胞对吉西他滨的化疗敏感性。Objective To explore the tumor suppressor CYLD in improving bladder cancer gemcitabine chemosensitivity. Methods The CYLD over-expressing plasmid was constructed and transfected into human bladder cancer cell lines T24 and 253 J,then the cells were divided into control group treated with liposome,empty plasmid transfection group and CYLD group. The effect of CYLD on the migration/invasion ability of bladder cancer cells was measured by Transwell assays. The chemosensitivity to gemcitabine was tested by CCK-8 assay. Autophagy-related proteins were detected by Western blotting,acridine orange staining,and transmission electron microscopy. Results Compared with the control group and empty plasmid transfection group,CYLD group had significantly decreased cell numbers in Transwell chambers（ P 〈 0. 05）; significantly reduced 50% cell growth inhibition in 24 h（ IC50）（P 〈 0. 05）; decreased expressions of LC3 and Beclin 1,but elevated expression of p62; decreased autophagy lysosomes and autophagic vacuoles.Conclusion CYLD can decrease the ability of migration/invasion and improve gemcitabine chemosensitivity by sup-pressing autophagy in bladder cancer cells.

关 键 词：膀胱肿瘤 吉西他滨 自噬 CYLD基因 化疗敏感性 

分 类 号：R574[医药卫生—消化系统]