氧化吲哚类化合物Z24的体内抑瘤活性及其血管生成抑制作用

摘要

目的从抗血管生成活性的角度,寻找新的抗肿瘤药物,研究Z24的体内抑瘤活性及其对血管内皮细胞的选择性抑制作用.方法 MTT法检测不同浓度的Z24作用72 h时对人肝癌细胞系BEL-7402及正常人胚肺二倍体细胞2BS的生长抑制作用,并从浓度-抑制率曲线求出IC50;台盼蓝拒染计数法检测不同浓度的Z24作用72 h时对人脐静脉内皮细胞(HUVEC)的生长抑制作用,从浓度-抑制率曲线求出IC50;小鼠S180, H22和裸小鼠皮下移植性人肝癌BEL-7402模型研究Z24的体内抑瘤作用.鸡胚尿囊膜(CAM)血管生成模型检测Z24的血管生成抑制活性.结果 MTT法测得Z24对BEL-7402生长抑制作用的IC50为106 μmol*L-1,对2BS生长抑制作用的IC50为116 μmol*L-1.台盼蓝拒染计数法测得Z24对HUVEC生长抑制作用的IC50为6.44 μmol*L-1.Z24可明显抑制鸡CAM新生血管的形成Z24 100 mg*kg-1可使S180, H22和裸小鼠人肝癌BEL-7402模型的肿瘤重量较对照组分别下降52.5%(n=10, P<0.01), 41.5%(n=10, P<0.01)和53.4%(n=6, P<0.01).Z24可显著抑制CAM的血管生成.结论 Z24对多种肿瘤动物模型均具有显著的体内抑瘤活性,对血管内皮细胞有选择性抑制作用, 并明显抑制CAM新生血管的生成.%AIM With the purpose of finding new antitumor drugs with anti-angiogenesis activity, the antitumor activity of Z24 in vivo and its anti-angiogenesis activity were investigated. METHODSMTT assay was used to determine the growth inhibitions of human hepatocellular carcinoma cell line BEL-7402 and pulmonary cells of fetus 2BS by Z24. Trypan-blue exclusion was used to measure the growth inhibition of human umbilical vein vascular endothelial cells (HUVEC) by Z24. Chorioallantoic membrane(CAM) assay was used to determine the anti-angiogenesis activity of Z24. Transplantable mouse sarcoma 180(S180), hepatoma 22 (H22) and human hepatocellular carcinoma cell line BEL-7402 models were used to evaluate the antitumor activity of Z24 in vivo. RESULTSThe IC50 values of Z24 for BEL-7402 and 2BS by MTT assay were found to be 106 μmol*L-1 and 116 μmol*L-1, respectively. The IC50 value of Z24 for HUVEC by trypan-blue exclusion assay was 6.44 μmol*L-1. Z24 at 100 mg*kg-1 inhibited the growth of subcutaneous S180, H22, and BEL-7402 tumors by 52.5%(n=10, P<0.01), 41.5%(n=10, P<0.01), and 53.4%(n=6, P<0.01), respectively. CONCLUSION These results suggest that Z24 present high antitumor activity in vivo, can selectively inhibit vascular endothelial cells, and have anti-angiogenesis activity on CAM.