基因转移FasL治疗人黑素瘤的实验研究  

FasL gene transfer in experimental treatment of human melanoma

作　　者：马文雄[1] 陈桂林[1] 韦永新[1] 惠国桢[1] 张世明[1] 周岱[1] 杜子威[1] 

机构地区：[1]苏州大学附属第一医院,江苏苏州215006

出　　处：《实用肿瘤杂志》2006年第2期111-114,共4页Journal of Practical Oncology

摘　　要：目的探讨体内外基因转移F as配体(F as-ligand,F asL)对恶性人黑素瘤细胞凋亡的影响。方法用携带人F asL cDNA的缺陷型重组腺病毒(A d-F asL),在体外转导两株黑素瘤细胞,并使其表达;通过流式细胞仪、RT-PCR法进行F as/F asL表达检测,TUNEL法及荧光显微镜相关凋亡检测、分析。建立人黑素瘤裸鼠模型,并对其进行体内疗效观察及病理学检查。结果流式细胞仪和RT-PCR检测两株黑素瘤细胞表面均表达F as,不表达F asL,而A d-F asL转导的两株黑素瘤细胞均能表达F asL;A d-F asL能显著诱导两株黑素瘤细胞在体外凋亡或抑制其生长。体内疗效观察黑素瘤荷瘤鼠模型治疗组瘤重(0.48±0.16)g与对照组瘤重(1.02±0.19)g相比,差异有显著性(P<0.05)。肿瘤组织形态学检查,治疗组可见肿瘤细胞凋亡坏死区及炎性细胞浸润。结论F asL基因重组腺病毒在体内外均具有显著诱导人黑素瘤细胞凋亡的效果。Objective To evaluate the effects of Fas ligand（FasL） gene transfer on apoptosis of malignant melanoma in vitro and in vivo. Methods Recombinant adenoviral vector containing human FasL cDNA（Ad-FasL） and a cytomegalovirus （CMV） promoter were constructed and transfected into two melanoma cell lines. The expression of Fas/FasL was identified with flow cytometry and RT-PCR. Tumor cell apoptosis both in culture and in nude mice model was examined with TUNEL method and fluorescence microscopy. Results RT-PCR and flow cytometric analysis showed the expression of Fas but no FasL on two melanoma cell lines. After transfection with Ad-FasL the tumor cells expressed high level of FasL; meanwhile the cell growth was suppressed and apoptosis was induced. In the Ad-FasL treatment group the tumor weighed （0. 48±0. 16）g and presented a significant difference with that of the control group （1.02±0. 19）g, （P〈0. 05）. The histopathological examination demonstrated necrosis areas, cell apoptosis and infiltration of inflammatory cells in tumor tissue of the treatment group. Conclusion Recombinant Ad-FasL transfection can induce the apoptosis of human melanoma cells in vitro and in vivo.

关 键 词：黑色素瘤/病理学 小鼠 裸 基因转移 脱噬作用 重组 遗传 肿瘤细胞 培养的 腺病毒科 膜糖蛋白类 

分 类 号：R73-3[医药卫生—肿瘤]