Ad-hING4联合^(125)Ⅰ粒子对裸鼠胰腺癌移植瘤的抑癌增效作用  

Cooperation of Ad-hING4 and ^(125)Ⅰ seed in tumor-suppression on human pancreatic cancer xenograft in nude mice

作　　者：翟红彦[1] 杨吉成[2] 盛伟华[2] 谢宇锋[2] 法逸华[1] 苏成海[1] 

机构地区：[1]苏州大学附属第一医院核医学科,苏州215006 [2]苏州大学基础医学系细胞与分子生物学教研室,苏州215006

出　　处：《核技术》2009年第12期940-946,共7页Nuclear Techniques

基　　金：苏州大学医学发展基金(EE122614)资助

摘　　要：本工作探讨腺病毒介导的人ING4基因(Ad-hING4)联合125I粒子对裸鼠胰腺癌移植瘤的抑癌增效作用及其可能的机制。将本室构建的Ad-hING4腺病毒感染QBI-293A细胞,扩增后获得高滴度的病毒。建立25只裸鼠胰腺癌PANC-1皮下移植瘤模型,分成PBS对照组、空病毒Ad组、125I粒子近距离放疗组、Ad-hING4基因治疗组、125I粒子和Ad-hING4联合治疗组,进行抑瘤治疗实验;此后每5天测量1次肿瘤体积,20天后处死,计算抑瘤率和金氏q值。常规病理切片观察细胞生长形态、组织损伤程度和范围,并进行凋亡细胞计数(AI);免疫组化SP法检测肿瘤标本中微血管密度(MVD)、生存素Survivin和活化的Caspase-3凋亡相关蛋白的表达。结果发现,125I粒子组、Ad-hING4组、联合治疗组抑瘤率分别达到34.19%(P<0.01)、31.50%(P<0.01)、67.15%(P<0.01),联合治疗组抑瘤率明显高于125I粒子和Ad-hING4治疗组(P<0.01);病理切片检查显示近粒子处肿瘤细胞变性坏死,远离粒子处可见存活肿瘤细胞;三个治疗组凋亡指数(AI)、Caspase-3阳性细胞数明显高于PBS组(P<0.05),且联合治疗组明显高于125I粒子和Ad-hING4治疗组(P<0.01);三个治疗组MVD值、Survivin阳性细胞明显低于PBS组(P<0.05),且联合治疗组明显低于125I粒子和Ad-hING4治疗组(P<0.01);Ad组与PBS组的各指标无显著性差异(P>0.05)。可见125I粒子、Ad-hING4可显著抑制裸鼠PANC-1胰腺癌移植瘤的生长,两者联用具有抑癌增效的协同作用,Ad-hING4有望作为一种新的放疗增敏剂;其抑瘤机制可能是通过下调Survivin和上调Caspase3的表达,以诱导肿瘤细胞凋亡、抑制肿瘤血管形成。This work is to investigate the combined tumor-suppression effect of Adenovirus-mediated human ING4 （Ad-hING4） and ^125Ⅰ seed on human pancreatic cancer xenograft and the possible mechanisms. Ad-hING4 recombinant adenovirus vector was transected into QBI-293A cells and high titre adenovirus was obtained. Subcutaneous tumor models were established with 25 nude mice with human pancreatic cancer cell line PANC-1. They were randomly divided into 5 groups： PBS control group, Ad carrier group, ^ 125Ⅰ seed brachytherapy group, Ad-hING4 gene treatment group, combined ^ 125Ⅰ seed and Ad-hING4 group. The tumor volumes were measured every 5 days after treatment, and were sacrificed on the 20^th day. The tumors were measured and weighed to determine the ratio of tumor-suppression and Jin-Shi q value. Morphological changes of tumor cells, the tissue injury and apoptotic index AI were examined on pathological sections. MVD, Survivin and Caspase3 were tested in immunohistochemistry. The results show that the tumor-suppressive ratio of the ^ 125Ⅰ seed group, Ad-hING4 group, combined treatment group were, respectively, 34.19%（P 〈 0.01）, 31.50%（P 〈 0.01）, and 67.15 % （P 〈 0.01） which was markedly higher than other two groups （P 〈0.01）. The pathological examination found degenerative necrosis at the site was nearby the seed but the living tumor cell still presented faraway from the seed. AI and Caspase3 positive ceils in the treatment groups were higher than PBS group significantly （P 〈 0.05）, and the combined treatment group was higher than other two treatment groups significantly （P〈0.01）. MVD and Survivin positive cells in the treatment groups were lower than PBS group significantly （P 〈 0.05）, and the combined treatment group was lower than other 2 treatment groups significantly （P 〈 0.01）, too. There was no significant difference between Ad group and PBS group in every detection index （P〉0.05）. It can be concluded that ^ 125Ⅰ seed and Ad-hING4 inhibit t

关 键 词：125I粒子 近距离治疗 hING4 胰腺肿瘤 裸鼠 基因治疗 放疗增敏剂 机制 

分 类 号：R817[医药卫生—影像医学与核医学]