曲古抑菌素A联合卡介苗对膀胱癌细胞的抑制作用及机制  

Inhibitory effect of Trichostatin A and Bacillus calmette-guerin on growth of bladder cancer cells

作　　者：田雨冬[1] 潘铁军[2] 叶章群 李功成[2] 

机构地区：[1]中科技大学同济医学院附属同济医院泌尿外科,武汉430030 [2]广州军区武汉总医院泌尿外科

出　　处：《中华实验外科杂志》2010年第3期282-284,共3页Chinese Journal of Experimental Surgery

基　　金：湖北省科技攻关计划资助项目（2007AA301815-4）

摘　　要：目的观察曲古抑菌素A（TSA）和卡介苗（BCG）及两者联合对膀胱癌细胞的影响，并探讨其作用机制。方法采用噻唑蓝（MTF）比色法检测细胞生长抑制率，流式细胞术（FCM）检测膀胱癌细胞凋亡的变化，逆转录-聚合酶链反应（RT—PCR）检测细胞FasmRNA、X连锁凋亡抑制蛋白（XIAP）mRNA表达的变化，Westernblot检测细胞Fas、XIAP蛋白水平的变化。结果TSA和BCG及两者联合能明显抑制膀胱癌细胞生长，呈时间和剂量依赖，相对中高剂量两者联用表现为协同作用（＋＋）。FCM检测示两者联用较单用凋亡比例明显增加，处理24b后，总凋亡率从（14．88±1．34）％（BCG）和（28．15±2．13）％（TSA）升高到（61．06±4．29）％（TSA＋BCG），差异有统计学意义（P〈0．01）；RT—PCR结果示TSA和BCG及两者联合处理能显著诱导FasmRNA的表达和显著抑制XIAPmRNA的表达，两者联合与单用比较差异有统计学意义（P〈0．05）；Westernblot进一步存蛋白水平证实了上述结果。结论TSA和BCG可通过诱导细胞凋亡而发挥体外抗膀胱癌作用，其作用机制可能涉及相关基因（Fas、XIAP）表达的调控。Objective To investigate the effects of Trichostatin A （TSA） and Bacillus calmetteguerin （BCG） on bladder cancer cells （BCC） and the mechanism. Methods Cell growth was measured by MTT assay. Cell apoptosis changes were examined by means of flow cytometry （FCM）. The mRNA expression of Fas and X-linked inhibitor of apoptosis protein （XIAP） was detected by reverse transcriptionpolymerase chain reaction （RT-PCR） , and the expression levels of Fas and XIAP protein were detected by Western blotting. Results TSA and BCG significantly inhibited the proliferation of BCC in a time-dependert and dose-dependent manner. When administered in moderate or high concentration, TSA combined with BCG demonstrated synergic effect （＋＋）. After treatment with TSA and BCG, total apoptosis was increased from （14.88±1.34）% （BCG） and （28.15±2.13）% （TSA） to （61.06±4.29）% （TSA＋ BCG） （P 〈0.01 ） , accompanied by increased Fas mRNA expression and decreased XIAP mRNA expression （P 〈 0.05 ）. The above results were further confirmed by Western blotting. Conclusion TSA and BCG can inhibit bladder cancer ceils growth in vitro through inducing cell apoptosis, which might be related to the expression of Fas and XIAP.

关 键 词：膀胱癌 曲古抑菌素A 卡介苗 脱噬作用 

分 类 号：R737.14[医药卫生—肿瘤]