Inhibition of Dual Specific Oncolytic Adenovirus on Esophageal Cancer via Activation of Caspases by a Mitochondrial-dependent Pathway  

作　　者：SU Jia-qiang CHI Bao-rong LI Xiao LIU Lei LIU Li-ming QI Yan-xin WANG Zhuo-yue JIN Ning-yi 

机构地区：[1]Department of Gastroenterology,The First Hospital of Jilin University,Changchun 130021,P.R.China [2]Genetic Engineering Laboratory of PLA,Academy of Military Medical Sciences of PLA,Changchun 130122,P.R.China [3]Department of Gastroenterology,People k Hospital of Heilongjiang Province,Harbin 150036,P.R.China [4]Jilin Academy of Agricultural Science and Technology,Jilin 132101,P.R.China

出　　处：《Chemical Research in Chinese Universities》2012年第3期465-471,共7页高等学校化学研究（英文版）

基　　金：Supported by the Genetically Modified Organisms Breeding Major Project of China(No.2009ZX08006-002B);the National Natural Science Foundation of China(Nos.81101140,81072210);the Key Technologies Research and Development Program of Jilin Province,China(Nos.10ZDGG007,201015166);the China Postdoctoral Science Foundation Funded Project(No.20100481057)

摘　　要：We investigated the anti-tumor effects of dual cancer specific-oncolytic adenovirus Ad-VP on esophageal cancer（EC）. The anti-tumor activity of Ad-VP was compared with that of the control recombinant adenoviruses （Ad-GP, Ad-Apoptin, Ad-EGFP） in human esophageal cancer cell EC-109 and human normal liver cell L02 in vitro. In 3-（4,5-dimethylthiazol-2-yl）-2,5-diphenyltetrazolium bromide（MTT） assays, the growth of EC-109 cells was slightly inhibited by Ad-GP, Ad-Apoptin and Ad-EGFE However, Ad-VP induced a significant cytotoxic effect. Infection of EC-109 cells with Ad-VP resulted in a significant induction of apoptosis of them in vitro, detected by 4＇,6-diamidino-2-phenylindole（DAPI） or acridine orange and ethidium bromide staining. The results of Western blot and flow cytometric assay indicate the loss of mitochondrial membrane potential（Aψm）, the release of eytochrome c and the activation of caspase-3, 6 and 7 in Ad-VP infected EC-109 cells. In contrast, all these assays show almost no effects of the recombinant adenoviruses on L02 cells. These results demonstrate that the treatment of tumors with Ad-VP selectively inhibits tumor growth and induces apoptosis of esophageal cancer cells. Ad-VP may provide a novel and powerful strategy for cancer gene therapy.We investigated the anti-tumor effects of dual cancer specific-oncolytic adenovirus Ad-VP on esophageal cancer（EC）. The anti-tumor activity of Ad-VP was compared with that of the control recombinant adenoviruses （Ad-GP, Ad-Apoptin, Ad-EGFP） in human esophageal cancer cell EC-109 and human normal liver cell L02 in vitro. In 3-（4,5-dimethylthiazol-2-yl）-2,5-diphenyltetrazolium bromide（MTT） assays, the growth of EC-109 cells was slightly inhibited by Ad-GP, Ad-Apoptin and Ad-EGFE However, Ad-VP induced a significant cytotoxic effect. Infection of EC-109 cells with Ad-VP resulted in a significant induction of apoptosis of them in vitro, detected by 4＇,6-diamidino-2-phenylindole（DAPI） or acridine orange and ethidium bromide staining. The results of Western blot and flow cytometric assay indicate the loss of mitochondrial membrane potential（Aψm）, the release of eytochrome c and the activation of caspase-3, 6 and 7 in Ad-VP infected EC-109 cells. In contrast, all these assays show almost no effects of the recombinant adenoviruses on L02 cells. These results demonstrate that the treatment of tumors with Ad-VP selectively inhibits tumor growth and induces apoptosis of esophageal cancer cells. Ad-VP may provide a novel and powerful strategy for cancer gene therapy.

关 键 词：APOPTIN Apoptosis ANTI-TUMOR Esophageal cancer Recombinant adenovirus 

分 类 号：Q784[生物学—分子生物学] Q782