论文部分内容阅读
Loss of (genomic) imprinting (LOI) of the insulin-like growth factor 2 gene (IGF2)is likely associated with the loss of activity of CTCF (an insulator of transcription)in human neoplasm, assuming as a result of increased IGF2 expression since the inactive CTCF cannot bind to the differentially methylated domains (DMD).In this study, combined expression of adenoviral vectors (Ad-EGFP and Ad-E1A) driven by H19 enhancer-DMD-H19 promoter complex was investigated and their effects on the tumor growth were assessed in vitro and in vivo.When infected with Ad-EGFP, the cancer cell lines with the LOI, such as HRT-18 cells and HT-29 cells, had the expression of the EGFP protein, whereas three cancer cell lines with the maintenance of imprinting (MOI) (HCT-116, MCF-7 and GES-1)had weak expression of EGFP.Furthermore, the expressed Ad-E1A significantly decreased cell viability and induced cell apoptosis only in HRT-18 and HT-29 cells in vitro, and effectively suppressed tumor development in HRT-18 and HT-29 xenograft in nude mice.It is concluded that this gene therapy vector is effective in the suppression of the growth of human colon cancer cells in vitro and in vivo, and that cancer gene therapy based on loss of IGF2 imprinting is an additional treatment option.