泛素特异性肽酶22诱导胰腺癌细胞对吉西他滨耐药的观察  

Effect of USP22 on gemcitabine chemoresistance in human pancreatic cancer cell

作　　者：王宛明[1] 董贾中[1] 管淑敏[1] WANG Wanming DONG Jiazhong GUAN Shuming(Department of Gastroenterology, Puyang People＇s Hospital, Puyang 457000, Henan, Chin)

机构地区：[1]河南省濮阳市人民医院消化科

出　　处：《中国临床药理学与治疗学》2017年第4期412-417,共6页Chinese Journal of Clinical Pharmacology and Therapeutics

摘　　要：目的:探讨泛素特异性肽酶22(ubiquitin specific peptidase 22,USP22)在胰腺癌吉西他滨耐药中的作用。方法:采用Western blot检测吉西他滨诱导不同胰腺癌细胞株对USP22表达情况的影响。利用胰腺癌SW1990亲本细胞株,构建吉西他滨耐药细胞株SW1990/Gem及USP22siRNA稳定表达细胞株(表示为SW1990-sh USP22、SW1990/Gem-sh USP22);采用CCK-8实验检测抑制USP22表达对胰腺癌细胞吉西他滨敏感性的影响。结果:1μmol/L或10μmol/吉西他滨诱导人胰腺癌PANC-1和SW1990细胞后,USP22表达均增高(P<0.05或P<0.01)。耐药细胞株SW1990/Gem中USP22蛋白表达显著高于SW1990亲本细胞株(P<0.01)。USP22 siRNA稳定表达细胞株SW1990-sh USP22,SW1990/Gem-sh USP22中USP22蛋白表达水平与相应对照组SW1990-NC,SW1990/Gem-NC相比,分别显著下调约65%(P<0.01)和60%(P<0.01)。SW1990-NC组和SW1990-sh USP22组对吉西他滨的IC50分别为(1 850.96±87.37)nmol/L和(534.83±49.68)nmol/L,差异具有统计学意义(P<0.01)。SW1990/Gem-sh USP22组对吉西他滨的IC50为(2 157.08±120.32)nmol/L,与SW1990/Gem-NC组(29 850.96±345.78)nmol/L相比,差异具有统计学意义(P<0.01);与SW1990-NC组(1 387.58±96.56)nmol/L相比,差异无统计学意义(P>0.05)。结论:吉西他滨可诱导胰腺癌细胞USP22表达增高。抑制USP22表达可增加胰腺癌细胞对吉西他滨的药物敏感性,并可有效逆转胰腺癌细胞对吉西他滨的耐药。本研究揭示胰腺癌细胞对吉西他滨耐药的新机制,为改善胰腺癌个体化化疗方案提供新思路。AIM： To evaluate the potential effect of USP22 on gemcitabine chemoresistance in pancreatic cancer cells. METHODS： USP22 expression was detected by Western blot in pancreatic cancer cell lines PANC-1 and SW1990 treated with gemcitabine. The ICso values of different pancreatic cancer ceils to gemcitabine were detected by cell counting kit 8 （CCK-8） assays. RESULTS ： USP22 expression was induced by certain dose of gemcit- abine treatment in pancreatic cancer cells. CCK-8 assay demonstrated that the ICs0 values in SW1990- NC group and SW1990-shUSP22 group were （1850.96 ± 87. 37） nmol/L and （534. 83 ± 49.68 ） nmol/L, respectively. Furthermore, the IC50 values in SW1990-NC, SW1990/Gem-NC and SW1990/Gem-shUSP22 groups were （1 387.58±96.56） nmol/L, （29 850.96 ±345.78 ） nmol/L and （ 2 157.08 ± 120.32 ） nmol/L, respectively. CONCLUSION： Gemcitabine treatment increases the expression of USP22 in pancreatic cancer cells. Knock-down USP22 expression could enhance the chemosensitivity to gemcitabine in pancreatic cancer cells, but also rescue the gemcitabine resistance in oancreatic cancer cells.

关 键 词：泛素特异性肽酶22 胰腺癌 吉西他滨 耐药 

分 类 号：R965.2[医药卫生—药理学]