新型伊立替康衍生物ZBH-1208的体外抗肿瘤活性及机制研究  

Study on anti-tumor activity and mechanism of novel Irinotecan derivatives ZBH-1208 in vitro

作　　者：赵静[1] 于鸿[2] 吴荻[3] 史卫国[4] 仲伯华[4] 刘菁[1] 张馨月[5] 赵大玮[6] 王学林[1] 

机构地区：[1]吉林大学动物医学学院人兽共患病研究所人兽共患病研究教育部重点实验室,吉林长春130062 [2]吉林省肿瘤防治研究所细胞生物研究室,吉林长春130012 [3]吉林大学第一医院肿瘤中心,吉林长春130021 [4]军事医学科学院毒物药物研究所,北京100850 [5]中国科学院长春应用化学研究所,吉林长春130022 [6]吉林省肿瘤医院乳腺科,吉林长春130012

出　　处：《中国实验诊断学》2015年第2期181-186,共6页Chinese Journal of Laboratory Diagnosis

基　　金：吉林省科技发展计划应用基础研究项目(20130102097JC);吉林省卫生厅研究项目(2012Z037)

摘　　要：目的研究新型伊立替康衍生物ZBH-1208体外对肿瘤细胞的生长抑制作用并初步探讨其作用机制。方法采用四甲基偶氮唑盐比色(MTT)法检测分析ZBH-1208对人宫颈癌HeLa细胞、人非小细胞肺癌A549细胞、人小细胞肺癌NCI-H446细胞、人乳腺癌MCF-7细胞、人结肠癌SW1116细胞、人胃腺癌SGC-7901细胞、人肝癌SMMC-7721细胞及人胚肾293细胞的生长抑制作用,计算IC50值;流式细胞术检测ZBH-1208对肿瘤细胞周期及活化Caspase-3表达的影响。结果 ZBH-1208对肿瘤细胞的生长具有抑制作用,呈剂量-时间依赖关系。ZBH-1208作用各肿瘤细胞后IC50值在0.002μmol/L-0.265μmol/L之间,而对照组伊立替康(CPT-11)的IC50值在0.464μmol/L-52.111μmol/L之间,两者相比较差异均有统计学意义(P<0.05)。流式细胞术检测结果显示,ZBH-1208诱导肿瘤细胞发生G2/M期阻滞,百分比到达90%以上;并且诱导活化形式Caspase-3表达增加。结论与CPT-11相比,新型化合物ZBH-1208具有高效低毒、起效快的特点,可使肿瘤细胞发生细胞周期阻滞,并诱导肿瘤细胞凋亡,具有进一步研究开发的价值。Objective To investigate the inhibition effect on the growth of tumor cells of novel Irinotecan derivatives ZBH-1208 in vitro and further probe its anticancer mechanisms.Methods MTT assay was used to evaluate the preliminary anti-tumor effect of ZBH-1208 on A549,NCI-H446,HeLa,SGC-7901,MCF-7,SW1116,SMMC-7721 and 293cell lines.Cytotoxicity for the tumor cells was assessed by the tumor cell growth inhibition rates and IC50.Flow cytometry analysis was performed to analyze the expression of Caspase-3and cycle distribution of the tumor cells treated with ZBH-1208.Results ZBH-1208 had significant anti-proliferation effects on A549,NCI-H446,HeLa,SGC-7901,MCF-7,SW1116,SMMC-7721 cell lines,and was dependence on concentration and time variant.IC50 of seven cancer cell treated with ZBH-1208 were significantly lower than that of CPT-11（P〈0.05）.Cell cycle of the tumor cells treated with ZBH-1208 were arrested in G2/M phase.The expression of active Caspase-3in the tumor cell was generally up-regulated.Conclusion Comparison with CPT-11and/or SN38,the novel compound ZBH-1208 was more efficient and lowertoxicity in significant inhibit growth of the tumor cells.ZBH-1208 play an important role in the apoptosis inducement of tumor cells by arresting the tumor cells cycle and would positive contribute to on further research in clinical treatment.

关 键 词：伊立替康 衍生物 细胞周期阻滞 细胞凋亡 

分 类 号：R96[医药卫生—药理学]