端粒酶抑制剂抑制鼠类肉瘤病毒癌基因突变肺癌细胞的恶性表型  

The telomerase inhibitor can inhibit the malignancy of lung cancer cells with kirsten rat sarcoma viral oncogene mutation

作　　者：尹岳松 史博文[1] 朱金芳[1] 张华[1] 高留伟 张彬[1] 王长利[1] 

机构地区：[1]天津医科大学肿瘤医院肺部肿瘤科国家肿瘤临床医学研究中心天津市“肿瘤防治”重点实验室,300060

出　　处：《中华实验外科杂志》2016年第5期1264-1267,共4页Chinese Journal of Experimental Surgery

摘　　要：目的 观察端粒酶抑制剂（BIBR1532）对含有鼠类肉瘤病毒癌基因（KRAS）突变肺癌细胞的影响.方法 利用慢病毒载体构建稳定表达KRAS第12外显子突变（所编码的氨基酸由甘氨酸突变为天冬氨酸,即G12D突变）的肺癌细胞株.Western blot检测G12D的表达水平.实时定量聚合酶链反应（Real-time PCR）法检测端粒酶活性.噻唑蓝（MTTT）法、划痕实验检测端粒酶抑制剂对表达G12D的肺癌细胞增殖、药物敏感性和迁移的影响.结果 成功建立了稳定表达KRAS-G12D的CALU3和H1299细胞株;BIBR1532抑制了过表达KRAS-G12D的CALU3和H1299细胞端粒酶活性（抑制率约为50％）;BIBR1532对KRAS-G12D诱导的促肺癌细胞增殖能力、促肺癌细胞迁移能力和化疗抗性（细胞对顺铂和紫杉醇的敏感性提高了10％ ～15％和5％～12％）都产生了明显抑制.结论 端粒酶抑制剂能够抑制KRAS-G12D突变肺癌细胞的增殖、迁移,提高KRAS-G12D突变肺癌细胞对化疗药物的敏感性.Objective To explore the effects of telomerase inhibitor BIBR1532 on lung cancer cells with kirsten rat sarcoma viral oncogene （KRAS） mutation.Methods Human lung cancer cells （CALU3/H1299） stably transfected with lentiviral vector-mediated KRAS-mutant （the encoded amino acid from glycine mutated to aspartic acid,G12D） expression were established and the telomerase activity and the expression levels of G12D were respectively detected by real-time quantitative polymerase chain reaction （Real-time PCR） and Western blotting.The proliferative activity,chemotherapy sensitivity and metastatic capability of cells were examined by methyl thiazol tetrazolium （MTI） and Scratch test.Results The telomerase activity level in KRAS-mutant lung cancer cells with telomerase inhibitors was more significantly decreased compared to KRAS wild type （KRAS-WT） lung cancer cells（the inhibition rates were about 50%）.Relative to KRAS-WT cells,the KRAS-mutant cells with BIBR1532 grew and migrated more slowly,moreover,the inhibition ratio was improved more greatly （cisplatin and taxol respectively increased 10%-15% and 5%-12%）.Conclusion The telomerase inhibitors could inhibit proliferative ability and metastatic capability,and increase chemotherapy sensitivity of KRAS-mutant and KRAS-WT lung cancer cells,but the variation of KRAS-mutant lung cancer cells was greater.

关 键 词：肺癌 鼠类肉瘤病毒癌基因突变 端粒酶抑制剂 

分 类 号：R734.2[医药卫生—肿瘤]