Effects of compound 209 on colorectal cancer cell HT-29 in vivo and in vitro  

化合物209对人结直肠癌细胞HT-29的体内和体外作用(英文)

作　　者：蒋晓[1] 袁霞[1] 楚明明[1] 郭维[1] 刘敬弢[1] 冉福香[1] 葛泽梅[2] 李润涛[2] 崔景荣[1] 

机构地区：[1]北京大学医学部天然药物及仿生药物国家重点实验室,北京100191 [2]北京大学医学部药学院化学生物学系,北京100191

出　　处：《Journal of Chinese Pharmaceutical Sciences》2013年第1期89-94,共6页中国药学（英文版）

基　　金：China International Science and Technology Cooperation Program for Key Projects (Grant No. 2008DFA31070)

摘　　要：Compound 209 is a newly synthesized dithiocarbamate derivative with antiproliferation activity in vitro, however, its antitumor effect in vivo and the underlying mechanisms have yet to be identified. We explored the antitumor effect of compound 209 and the possible mechanisms for its inhibition of the growth of HT-29 xenograff tumor and proliferation of HT-29 cells. Cell proliferation was evaluated with SRB assay in vitro. The results showed that compound 209 had significant antiproliferation activity on HT-29 cells. Furthermore, the xenograff HT-29 nude mouse model was used to study the antitumor effect of compound 209 in vivo. We found that compound 209 significantly inhibited tumor growth and did not cause loss of body weight or leukocytopenia. Analysis by flow cytometry indicated that compound 209 arrested HT-29 cell cycle in G~ phase. Western blotting analysis suggested that compound 209 increased the expression of p27, cyclin E, CDK2, cyclin D1 and CDK4. These results demonstrated the antitumor effect of compound 209 and its potential use as an anticancer drug.化合物209是一个新合成的氨基二硫代甲酸酯类化合物,它在体外水平可以抑制肿瘤细胞的增殖,但是化合物209的体内抗肿瘤作用及其抗肿瘤机制并不明确。本文探究了化合物209对人结直肠癌细胞HT-29的作用并初步探讨了相关机制。体外研究表明,化合物209可以显著抑制HT-29细胞的增殖;体内研究结果表明,化合物209可以显著抑制裸鼠HT-29移植瘤的生长,但是对裸鼠体重和白细胞无影响。流式细胞分析实验结果表明,化合物209可将HT-29细胞阻滞于细胞周期的G1期。同时,化合物209能上调体外培养HT-29细胞中p27,cyclin E,CDK2,cyclin D1和CDK4的表达。在体内瘤组织中上述蛋白表达情况与体外实验结果一致。这些结果说明,化合物209具有较好的抗肿瘤活性,其抗肿瘤作用与细胞周期阻滞及其相关蛋白的表达变化有关。

关 键 词：DITHIOCARBAMATE Compound 209 Cell cycle Cell cycle-related proteins HT-29 cell line 

分 类 号：R735.3[医药卫生—肿瘤]