title: Adenovirus-mediated ING4/IL-24 double tumor suppressor gene co-transfer             enhances antitumor activity in human breast cancer cells.
abstract: Cancer gene therapy represents a new and promising therapeutic modality             for various types of cancer. Two or more anti-oncogenes carried by a single vector             could theoretically improve treatment efficacy, reduce side-effects from vectors,             and have a satisfactory clinical application prospect; however, this has seldom             been studied in breast cancer. The inhibitor of growth 4 (ING4), as a member of             the inhibitor of growth tumor suppressor family has potent inhibitory effects             on a variety of tumors. Interleukin‑24 (IL-24) has also shown broad spectrum and             tumor-specific antitumor activities. In this study, we aimed to prove the enhanced             antitumor activity of adenovirus-mediated ING4/IL-24 double tumor suppressor gene             co-transfer in human breast cancer cells. We assessed the combined effect of the             ING4/IL-24 bicistronic adenovirus (Ad-ING4-IL-24) in vitro and in vivo on MDA-MB-231             human breast cancer cells by detecting and comparing the apoptotic status in the             bicistronic anti-oncogene group (Ad-ING4-IL-24) and in the ING4 or IL-24 single             anti-oncogene groups, and also investigated the possible underlying mechanism.             Our results showed that the bicistronic adenovirus-mediated ING4 and IL-24 co-expression             induced additive growth suppression and apoptosis as well as an overlapping effect             on the upregulation of p21, p27 and Bax, and the downregulation of Bcl-2 and survivin             in MDA-MB‑231 human breast cancer cells in vitro or in vivo. Moreover, Ad-ING4-IL-24             treatment additively reduced CD34 expression and the microvessel density in MDA-MB-231             xenografted tumors in athymic nude mice, which correlated with the decreased expression             of the vascular endothelial growth factor. The enhanced antitumor activity on             breast cancer elicited by Ad-ING4-IL-24 was closely associated with the activation             of the apoptotic pathways and the additive inhibition of tumor angiogenesis.
authors: Shanghai Tenth People's Hospital, Tongji University School of Medicine, Shanghai 200072, PR China.
authors: Yaodong
authors: Y
authors: Zhao
authors: Zhengyi
authors: Z
authors: Li
authors: Weihua
authors: W
authors: Sheng
authors: Jingchen
authors: J
authors: Miao
authors: Jicheng
authors: J
authors: Yang
mesh_terms: D000256:Adenoviridae / Q000235:genetics; D000818:Animals; D017209:Apoptosis / Q000235:genetics; D001943:Breast Neoplasms / Q000235:genetics* / Q000473:pathology / Q000628:therapy; D018797:Cell Cycle Proteins / Q000235:genetics*; D005260:Female; D005786:Gene Expression Regulation; D015972:Gene Expression Regulation, Neoplastic; D018014:Gene Transfer Techniques; D016147:Genes, Tumor Suppressor; D015316:Genetic Therapy / Q000379:methods*; D018398:Homeodomain Proteins / Q000235:genetics*; D006801:Humans; D007378:Interleukins / Q000235:genetics*; D051379:Mice; D008819:Mice, Nude; D009389:Neovascularization, Pathologic / Q000235:genetics; D014407:Tumor Cells, Cultured; D025521:Tumor Suppressor Proteins / Q000235:genetics*; D015854:Up-Regulation; D042461:Vascular Endothelial Growth Factor A / Q000235:genetics; D023041:Xenograft Model Antitumor Assays; D051028:bcl-2-Associated X Protein / Q000235:genetics; D000099180:Interleukin-24
chemical_list: D018797:Cell Cycle Proteins; D018398:Homeodomain Proteins; D007378:Interleukins; D025521:Tumor Suppressor Proteins; D042461:Vascular Endothelial Growth Factor A; D051028:bcl-2-Associated X Protein; D000099180:Interleukin-24; C494826:BAX protein, human; C483230:ING4 protein, human; C467484:VEGFA protein, human