瘤内注射β干扰素基因转染的人骨髓间充质干细胞对前列腺癌皮下移植瘤的治疗作用  

Gene therapy of prostate cancer xenograft by intra-tumoral injection of human Mesenchymal Stem Cells transfected with Interferon-beta gene

作　　者：詹以安[1] 王共先[1] 桑海明[1] 胡红林[2] 汪泱[1] 傅斌[1] 

机构地区：[1]南昌大学第一附属医院泌尿外科研究所,江西南昌330006 [2]南昌大学第二附属医院泌尿外科,江西南昌30006

出　　处：《中国现代医学杂志》2011年第30期3763-3767,共5页China Journal of Modern Medicine

基　　金：国家自然科学基金资助项目(No:30560153)

摘　　要：目的观察人β干扰素(IFN-β)基因修饰的人骨髓间充质干细胞(hMSCs)治疗人前列腺癌皮下移植瘤的作用。方法构建人IFN-β基因腺病毒表达载体Ad-IFN-β,体外转染hMSCs,使用4,6-联脒-2-苯基吲哚(DAPI)标记表达IFN-β的hMSCs(IFN-β-hMSCs)。应用人前列腺癌细胞株PC-3异种皮下种植建立前列腺癌动物模型,IFN-β-hMSCs瘤内注射入小鼠模型体内,收集肿瘤和肝、肺、脾、肾等脏器作冰冻切片和石蜡切片,荧光显微镜下观察肿瘤及各脏器中IFN-β-hMSCs的分布情况,记录IFN-β-hMSCs瘤内注射后荷瘤小鼠肿瘤大小及生存期。结果瘤内注射IFN-β-hMSCs后14 d,前列腺癌组织冰冻切片和石蜡切片中均可见DAPI标记的IFN-β-hMSCs,而肝、肺、脾、肾等脏器的切片中均未见IFN-β-hMSCs的存在。瘤内注射IFN-β-hMSCs可延长荷瘤鼠的生存期,抑制肿瘤的生长,实验组与对照组间差异有统计学意义(P<0.05)。结论 IFN-β-hMSCs在体内能够抑制前列腺癌移植瘤的生长,延长荷瘤鼠的生存期。[Objective]To investigate the effect of gene therapy for prostate cancer xenograft by intra-tumoral injection of human mesenchymal stem cells（hMSCs） transfected with Interferon-beta（IFN-β） gene.[Methods] Adenovirus vector containing human IFN-βgene was constructed and transfected into hMSCs in vitro.IFN-β-expressing mesenchymal stem cells（IFN-β-hMSCs） 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-hMSCs were intra-tumoral injected into the 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-hMSCs in vivo by fluorescence microscope.The weight of the tumor and the survival time of mice were observed to evaluate the experimental efficacies of IFN-β-hMSCs in the treatment of prostate cancer.[Results]IFN-α-hMSCs with blue nuclei were distributed extensively in the tumors,but no blue nucleus was seen in the livers,lungs,spleens and kidneys. Injection of IFN-β-MSCs can significandy reduce tumor weight and increase animal survival compared with controls （P〈0.05）.[Conclusion]Intra-tumoral injection of IFN-β-hMSCs can inhibits the tumor growth and increase animal survival of PC-3 xenografts in the SCID mice,and these engineered hMSCs can be exploited to therapeutic advantage against prostate cancer.

关 键 词：前列腺肿瘤 癌 骨髓间充质干细胞 Β干扰素 基因治疗 

分 类 号：R737.25[医药卫生—肿瘤] R318.16[医药卫生—临床医学]