Interferon-beta gene engineered human mesenchymal stem cells in the treatment of human prostate cancer xenograft in mouse model

Abstract

Objective To investigate the effect of human interferon-beta (IFN-β) gene engineered human mesenchymal stem cells (hMSC) in the treatment of human prostate cancer xenograft in nude mice.Methods An adenovirus vector containing human IFN-β gene was constructed and transfected into hMSC in vitro.IFN-β-expressing mesenchymal stem cells (IFN-β-hMSC) were labeled with 4,6-diamidino-2-phenylindole (DAPI).The human prostate cancer cell line PC-3 were injected into the flank or axillary of severe combined immunodeficiency (SCID) mice subcutaneously to establish human prostate cancer xenograft models.IFN-β-hMSC were injected into the tail vein of mice bearing human prostate cancer xenografts.The tumors,livers,lungs,spleens and kidneys were harvested.Frozen sections and paraffin sections were used to observe the distribution of IFN-β-hMSC in vivo by fluorescence microscope.Mice were divided into seven groups of six animals randomly,IFN-β-hMSC (2 × 106,2 × 105 ) as treatment group,Ad-hMSC,unmodified hMSC,Ad-IFN-β,Recombinant IFN-β,and NS as control group.The weight of the tumor and the survival time of mice were observed to evaluate the experimental efficacies of IFN-β-hMSC in the treatment of prostate cancer. Results IFN-β-hMSC with blue nuclei were distributed extensively in the tumors,but no blue nucleus was seen in the livers,lungs,spleens and kidneys.After treating,the weights of the tumour masses from mice were (1.35 ±0.28) g,(1.43±0.41) g,(3.49 ±0.25)g,(3.58±0.30)g,(3.30 ±0.24) g,(3.32 ±0.25) g,(3.32 ±0.47) g in the IFN-β-hMSC (2 ×106),IFN-β-hMSC (2 ×105),Ad-hMSC,unmodified hMSC,Ad-IFN-β,Recombinant IFN-β,and NS group,the median survival time from mice were 91 d,87 d,57 d,59 d,62 d,61 d,61 d in the IFN-β-hMSC (2 × 106),IFN-β-hMSC (2 × 105),Ad-hMSC,unmodified hMSCs,Ad-IFN-β,Recombinant IFN-β,and NS group,respectively.Injection of IFN-β-MSC can significantly reduce tumor weight and increase animal survival compared with controls ( P ＜ 0.05 ). Conclusion IFN-β-hMSC can migrate to prostate cancer microenviroment in vivo,and injection of IFN-β-MSC can significantly reduce tumor weight and increase animal survival. Key words: Prostatic neoplasms; Carcinoma; Human mesenchymal stem cell; Interferon beta; Gene therapy