title: Gene therapy for human colorectal cancer cell lines with recombinant adenovirus 5 based on loss of the insulin-like growth factor 2 imprinting.
abstract: The recombinant oncolytic adenovirus is a novel anticancer agent to replicate selectively in colon cancer cell lines. Loss of imprinting (LOI) of insulin-like growth factor 2 (IGF2) gene is an epigenetic abnormality phenomenon. We utilized the IGF2 LOI in gene therapy for the malignant tumor cell lines. We investigated the tumoricidal effects of IGF2 LOI on four cell lines by oncolytic adenovirus, and constructed novel adenovirus vectors Ad312-E1A and Ad312-EGFP. The expression of E1A was monitored by real-time PCR and western blot analysis. The viability and apoptosis of colorectal cells infected with Ad312-E1A were tested by CCK-8 and flow cytometry. In addition, we established a colorectal cancer model in nude mice. The results showed that HCT-8 and HT-29 with IGF2 LOI were infected with Ad312-EGFP and then produced the EGFP. Nevertheless, SW480 and GES-1, which were IGF2 MOI, did not produce the EGFP. The Ad312-E1A obviously reduced the cell viability and induced apoptosis in HCT-8 and HT-29 in vitro, and successfully suppressed tumor growth in HT-29 xenografts in nude mice. In summary, the conditionally replicative adenovirus with loss of IGF2 imprinting system has a positive effect on gene therapy.
authors.affiliation: Department of Life Sciences, Nanjing Normal University, Nanjing, Jiangsu 210006, P.R. China.
authors.forename: Huiling
authors.initials: H
authors.lastname: Sun
authors.affiliation: Central Laboratory, Nanjing First Hospital, Nanjing Medical University, Nanjing, Jiangsu 210006, P.R. China.
authors.forename: Yuqin
authors.initials: Y
authors.lastname: Pan
authors.affiliation: Central Laboratory, Nanjing First Hospital, Nanjing Medical University, Nanjing, Jiangsu 210006, P.R. China.
authors.forename: Bangshun
authors.initials: B
authors.lastname: He
authors.affiliation: Central Laboratory, Nanjing First Hospital, Nanjing Medical University, Nanjing, Jiangsu 210006, P.R. China.
authors.forename: Qiwen
authors.initials: Q
authors.lastname: Deng
authors.affiliation: Department of Life Sciences, Nanjing Normal University, Nanjing, Jiangsu 210006, P.R. China.
authors.forename: Rui
authors.initials: R
authors.lastname: Li
authors.affiliation: Central Laboratory, Nanjing First Hospital, Nanjing Medical University, Nanjing, Jiangsu 210006, P.R. China.
authors.forename: Yeqiong
authors.initials: Y
authors.lastname: Xu
authors.affiliation: Department of Life Sciences, Nanjing Normal University, Nanjing, Jiangsu 210006, P.R. China.
authors.forename: Jie
authors.initials: J
authors.lastname: Chen
authors.affiliation: Central Laboratory, Nanjing First Hospital, Nanjing Medical University, Nanjing, Jiangsu 210006, P.R. China.
authors.forename: Tianyi
authors.initials: T
authors.lastname: Gao
authors.affiliation: Medical College, Southeast University, Nanjing, Jiangsu 210009, P.R. China.
authors.forename: Houqun
authors.initials: H
authors.lastname: Ying
authors.affiliation: Central Laboratory, Nanjing First Hospital, Nanjing Medical University, Nanjing, Jiangsu 210006, P.R. China.
authors.forename: Feng
authors.initials: F
authors.lastname: Wang
authors.affiliation: Central Laboratory, Nanjing First Hospital, Nanjing Medical University, Nanjing, Jiangsu 210006, P.R. China.
authors.forename: Xian
authors.initials: X
authors.lastname: Liu
authors.affiliation: Central Laboratory, Nanjing First Hospital, Nanjing Medical University, Nanjing, Jiangsu 210006, P.R. China.
authors.forename: Shukui
authors.initials: S
authors.lastname: Wang
mesh_terms: D017500:Adenovirus E1A Proteins / Q000235:genetics / Q000378:metabolism; D000818:Animals; D045744:Cell Line, Tumor; D002470:Cell Survival; D015179:Colorectal Neoplasms / Q000235:genetics / Q000378:metabolism / Q000628:therapy*; D000229:Dependovirus / Q000235:genetics / Q000378:metabolism*; D015316:Genetic Therapy / Q000379:methods*; D005822:Genetic Vectors / Q000008:administration & dosage / Q000235:genetics / Q000378:metabolism; D018392:Genomic Imprinting; D057809:HEK293 Cells; D019073:HT29 Cells; D006801:Humans; D007335:Insulin-Like Growth Factor II / Q000235:genetics*; D051379:Mice; D008819:Mice, Nude; D050130:Oncolytic Virotherapy / Q000379:methods*; D050504:Oncolytic Viruses; D023041:Xenograft Model Antitumor Assays
chemical_list: D017500:Adenovirus E1A Proteins; C035170:IGF2 protein, human; D007335:Insulin-Like Growth Factor II