title: Radiosensitivity by ING4-IL-24 bicistronic adenovirus-mediated gene cotransfer on human breast cancer cells.
abstract: Breast cancer is a common malignancy among women and is associated with poor 5-year survival rates. Gene radiotherapy, that is, gene therapy combined with radiotherapy, has been extensively studied as a new mode of therapy, but most studies have assessed only one gene. Here, we inserted two anti-oncogenes, ING4 (inhibitor of growth family member 4) and interleukin-24 (IL-24), in the same bicistronic adenovirus vector and explored the effect of dual-gene therapy combined with radiotherapy on breast cancer cells. Flow cytometry assays showed that adenovirus-mediated ING4 and IL-24 expression could suppress growth, promote apoptosis and induce G2/M cell-cycle arrest in MDA-MB-231 cells. Moreover, animal model studies demonstrated that the combination of ING4/IL-24 gene therapy and radiotherapy significantly suppressed cell proliferation and inhibited tumor growth (P<0.05). Mechanistically, the pro-apoptotic response likely involved the upregulation of Bax and Caspase-3 and the downregulation of Bcl-2. Thus, this study indicates that the co-expression of the two anti-oncogenes, ING4 and IL-24, could significantly promote radiotherapy sensitivity in MDA-MB-231 breast cancer cells.
authors.affiliation: Shanghai Tenth People's Hospital, Tongji University School of Medicine, Shanghai, China.
authors.forename: Y
authors.initials: Y
authors.lastname: Zhao
authors.forename: Z
authors.initials: Z
authors.lastname: Li
authors.forename: W
authors.initials: W
authors.lastname: Sheng
authors.forename: J
authors.initials: J
authors.lastname: Miao
authors.forename: J
authors.initials: J
authors.lastname: Yang
mesh_terms: D000256:Adenoviridae / Q000235:genetics*; D000818:Animals; D017209:Apoptosis; D051017:Apoptosis Regulatory Proteins / Q000378:metabolism; D001943:Breast Neoplasms / Q000473:pathology / Q000628:therapy*; D059447:Cell Cycle Checkpoints; D018797:Cell Cycle Proteins / Q000096:biosynthesis / Q000235:genetics*; D045744:Cell Line, Tumor; D049109:Cell Proliferation; D003131:Combined Modality Therapy; D005260:Female; D015870:Gene Expression; D015316:Genetic Therapy; D018398:Homeodomain Proteins / Q000096:biosynthesis / Q000235:genetics*; D006801:Humans; D007378:Interleukins / Q000096:biosynthesis / Q000235:genetics*; D051379:Mice; D008819:Mice, Nude; D011836:Radiation Tolerance / Q000235:genetics*; D014161:Transduction, Genetic; D047368:Tumor Burden; D025521:Tumor Suppressor Proteins / Q000096:biosynthesis / Q000235:genetics*; D023041:Xenograft Model Antitumor Assays; D000099180:Interleukin-24
chemical_list: D051017:Apoptosis Regulatory Proteins; D018797:Cell Cycle Proteins; D018398:Homeodomain Proteins; D007378:Interleukins; D025521:Tumor Suppressor Proteins; D000099180:Interleukin-24; C483230:ING4 protein, human