β干扰素基因修饰的人骨髓间充质干细胞治疗前列腺癌小鼠移植瘤的实验研究  

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

作　　者：詹以安[1] 王共先[1] 汪泱[1] 傅斌[1] 刘伟鹏[1] 胡红林[2] 

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

出　　处：《中华泌尿外科杂志》2012年第6期459-463,共5页Chinese Journal of Urology

基　　金：国家自然科学基金（30560153）

摘　　要：目的探讨人β干扰素（interferon—beta，IFN—β）基因修饰的人骨髓间充质干细胞（human mesenchymal stem cell，hMSC）对人前列腺癌小鼠移植瘤的治疗作用。方法构建人IFN-β基因腺病毒表达载体Ad—IFN—β，体外转染hMSC，使用4，6-联脒-2-苯基吲哚（DAPI）标记表达IFN—β的hMSC（IFN·β-hMSC）。应用人前列腺癌PC-3细胞株皮下种植建立小鼠前列腺癌动物模型，将IFN—β—hMSC经尾静脉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—hMSC的分布情况。42只小鼠随机分为治疗组：IFN—β-hMSC（2×10^6，2×10^5）组；对照组：Ad—hMSC组、hMSC组、Ad-IFN-β组、重组IFN—β组、生理盐水组，每组6只。记录各组尾静脉注射后荷瘤小鼠肿瘤大小及生存期。结果IFN—β-hMSC注射后14d，荷瘤小鼠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-hMSC，而肝、肺、脾、肾等脏器的切片中均未见IFN-β-hMSC的存在。肿瘤质量：IFN—β—hMSC（2×10^5）治疗组（1．35±0．28）g、IFN—β—hMSC（2×10^5）组（1．43±0．41）g，与对照Ad—hMSC组（3．49±0．25）g、hMSC组（3．58±0．30）g、Ad—IFN—β组（3．30±0．24）g、重组IFN-p组（3．32±0．25）g、生理盐水组（3．32±0．47）g比较差异均有统计学意义（P〈0．05）；IFN-β-hMSC（2×10^6）治疗组中位生存时间91d、IFN-β-hMSC（2×10^5）组87d，与对照Ad-hMSC组57d、hMSC组59d、Ad—IFN—β组62d、重组IFN—β组61d、生理盐水组61d比较差异有统计学意义（P〈0．05）。结论IFN—β—hMSC在体内具有向前列腺癌微环境聚集转移的特性，且能够抑制前列腺癌移植瘤的生长．延长荷瘤鼠的牛存期。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 ceils （IFN-β-hMSC） were labeled with 4, 6-diamidino-2-pheny- lindole （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-I3-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 × 10^6, 2 × 10^5） as treatment group, Ad-hMSC, unmodi-fied 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 effieaeies of IFN-β-hblSC 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-13-hMSC （2 ± 106） , IFN-β-hMSC （2 × 10^5）, 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 × 10^6） , IFN-β-hM- SC （2 × 10^5）, Ad-hMSC, unmodified hMSCs, Ad-IFN-β, Recombinant IFN-β, and NS group, respectively. Injection of IFN-β-MSC can signific

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]