人α-甘露糖苷酶Man2c1转基因对移植性肿瘤在小鼠体内生长和转移的影响  

Effects of Human α-mannosidase Man2c1 Transgene on Growth and Metastasis of Transplanted Tumor in Mice

作　　者：蒋东东[1] 刘玉琴[1] 顾蓓[1] 向志光[1] 田云[1] 周异群[1] 鞠吉雨[1] 刘音[1] 张连峰[2] 朱立平[1] 

机构地区：[1]中国医学科学院北京协和医学院基础医学院免疫学系,北京100005 [2]中国医学科学院实验动物研究所,北京100005

出　　处：《中国医学科学院学报》2007年第4期528-532,共5页Acta Academiae Medicinae Sinicae

基　　金：国家重点基础研究发展计划项目(973计划)(2001CB510004);国家高技术研究发展计划项目(863项目)(2002BA711A03)~~

摘　　要：目的研究人α-甘露糖苷酶(hMan2c1)转基因对小鼠移植性肿瘤生长、转移的影响。方法接种肝癌细胞H22或肉瘤细胞S180于野生型ICR小鼠和3个系的转基因小鼠(28、35和54号)右侧腋窝皮下,连续测量肿瘤体积。分别于接种细胞第9天和第10天处死小鼠,称重肿瘤。分别对肿瘤组织和肺组织进行HE染色。用Tris-NH4Cl破碎脾脏中的红细胞,以Yac-1细胞为靶细胞,检测脾脏中自然杀伤(NK)细胞的活性。结果接种于3个系的转基因小鼠的H22肿瘤或S180肿瘤的体积及重量均显著高于野生型小鼠(P<0.05)。绝大多数转基因小鼠的肿瘤向周围组织侵袭,而野生型小鼠的肿瘤几乎均有包膜。54、35和28号转基因小鼠的H22肿瘤肺转移率分别为30%(3/10)、50%(5/10)和30%(3/10),野生型小鼠的肿瘤肺转移率为10%(1/10);54、35和28号转基因小鼠的S180肿瘤肺转移率分别为16.7%(1/6)、50%(3/6)和33.3%(2/6),野生型小鼠的肿瘤肺转移率为0(0/10)。转基因小鼠脾脏的NK细胞活性与野生型小鼠比较差异无显著性(P>0.05)。结论hMan2c1转基因促进移植性H22肿瘤及S180肿瘤在ICR小鼠的生长、侵袭和转移,hMan2c1转基因对小鼠脾脏NK细胞的活性无影响。Objective To study the effect of human α-mannosidase Man2c1 transgene on tumor growth and metastasis in mice. Methods Hepatoma cell H22 or squamous epithelial carcinoma cell S180 was subcutaneously inoculated into the right armpit of mice （wild type mice and 28#, 35#, and 54# transgenic mice）. Tumor size was measured every week. Mice were sacrificed on day 9 or 10 and then the tumors were exercised and weighted. Tumors and lungs were fixed in formaldehyde and sectioned. The sections were stained with hematoxylin/eosin and examined under microscope. The red blood ceils in spleen were destroyed by Tris- NH4Cl. Natural killer （NK） cell activity was detected with Yac-1 cell as target. Results H22 and S180 tumors grew faster in all the three transgenic mice （28#, 35#, and 54#） than in wild type mice. The average size and weight of tumors between the transgenic mice and wild type mice were significantly different （ P 〈 0. 05 ）. Most tumors in the transgenic mice invaded the surrounding tissues. In contrast, nearly all the tumors in wild type mice were capsulized. Three of 10 28# transgenic mice, 5 of 10 35# transgenic mice, 3 of 10 54# transgenic mice, and 1 of 10 wild type mice showed lung metastasis of H22 tumor. Two of 6 28# transgenic mice, 3 of 6 35# transgenic mice, 1 of 6 54# transgenic mice, and 0 of 6 wild type mice showed lung metastasis of S180 tumor. No difference of NK activity in spleen cells was observed between the transgenic mice and wild type mice. Conclusions hMan2c1 transgene promotes growth, invasion, and metastasis of transplanted H22 and S180 tumors in mice. hMan2c1 transgene does not affect NK activity in splenocytes.

关 键 词：人α-甘露糖苷酶 转基因小鼠 肿瘤 自然杀伤细胞活性 

分 类 号：R73-37[医药卫生—肿瘤]