CRCU

Chemical Research in Chinese Universities ›› 2012, Vol. 28 ›› Issue (3): 465-471.

• Articles • Previous Articles     Next Articles

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

SU Jia-qiang1,2,3, CHI Bao-rong1, LI Xiao1,2, LIU Lei1,2, LIU Li-ming1,2,4, QI Yan-xin2, WANG Zhuo-yue2, JIN Ning-yi2   

  1. 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’s Hospital of Heilongjiang Province, Harbin 150036, P. R. China;
    4. Jilin Academy of Agricultural Science and Technology, Jilin 132101, P. R. China
  • Received:2011-11-25 Revised:2011-12-29 Online:2012-05-25 Published:2012-05-03
  • Contact: JIN Ning-yi E-mail:ningyik@126.com
  • Supported by:

    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) and the China Postdoctoral Science Foundation Funded Project(No. 20100481057).

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Abstract: 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-EGFP. 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(ΔΨm), the release of cytochrome 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.

Key words: Apoptin, Apoptosis, Anti-tumor, Esophageal cancer, Recombinant adenovirus