The Experimental Study On Antitumor Effect Of Interferon-belta CDNA Engineered Human Bone Marrow Mesenchymal Stem Cells To Prostate Cancer Cell Line PC-3

Objective: To observe the effects of human interferon-beta gene cDNA engineered human bone marrow mesenchymal stem cells(hMSCs) on the growth of prostate cancer cell line PC-3 in vivo,and explore the feasibility of hMSCs as vehicles for interferon-beta delivery into prostate cancer.Methods: The human prostate cancer cell line PC-3 were injected into the axillary of SCID mice subcutaneously to establish human prostate cancer xenograft models. hMSCs were harvested from donor's ribs of human cadaver renal transplantation and separated by density gradient centrifuge. hMSCs between passages 4 to 6 were labeled with CM-DiI. CM-DiI-labeled hMSCs were injected into the bearing cancer SCID mice by tail vein of labeled MSCs or tumor. The mice were killed and their tumors,livers,lungs,spleens and kidneys were harvested.Frozen sections and paraffin sections were used to observe the distribution of exogenous CM-DiI-labeled hMSCs in vivo by fluorescence microscope.The adenoviral expression vector containing huIFN-βgene(Ad-IFN-β) was constructed and transfected into hMSCs.The human prostate cancer cell line PC-3 were injected into severe combined immunodeficiency mouse(SCID) subcutaneously to establish human prostate cancer xenograft models.IFN-β-hMSCs were injected into the bearing cancer SCID mice by tail vein or intra-tumor.We observed the influence of IFN-β-hMSCs on the tumor or mice'survival and evaluated the effects of prostate cancer in response to IFN-β-hMSCs in vivo.Results: In SCID mice injected with PC-3 subcutaneously,the tumor take rate was91.7%.The tumors were identified by pathology After injection IFN-β-hMSCs into bearing cancer SCID mice by tail vein,IFN-β-hMSCs could migrate to prostate cancer microenviroment in vivo.But no IFN-β-hMSCs was seen in the lungs,livers,spleens,kidneys and muscles.Compared with control mice,injection of IFN-β-hMSCs by tail vein or intra-tumor could prolong mice'survival and inhibit the growth of prostate cancer. There was significant difference between experiment group and control group(P<0.001).Conclusions: The hMSCs can express IFN-βsuccessfully after huIFN-βgene transfection. IFN-β-hMSCs can migrate to prostate cancer microenviroment in vivo. IFN-β-hMSCs can inhibit the growth of prostate cancer significantly and prolong mice'survival in vivo, which may develop a new strategy about gene therapy in prostate cancer.