Survivin基因反义寡核苷酸与大肠癌血管形成的实验研究  

Survivin ASODN suppresses vasiformation in xenograft of colorectal cancer cells in nude mice

作　　者：李瑞[1] 黄宗海[1] 姚航[1] 厉周[1] 李强[1] 

机构地区：[1]南方医科大学珠江医院普通外科,广州510282

出　　处：《第三军医大学学报》2009年第13期1272-1274,共3页Journal of Third Military Medical University

摘　　要：目的研究Survivin反义寡核苷酸(antisense oligonucleotide,ASODN)对人大肠癌裸鼠移植瘤的细胞凋亡及血管形成的影响。方法建立裸鼠人大肠癌模型,将成瘤后的裸小鼠分为空白对照组、脂质体转染对照组、脂质体SODN对照组和脂质体ASODN组。测定瘤质量并计算移植瘤抑制率,瘤组织进行HE染色,用S-P法染色检测微血管密度(MVD),TUNEL法检测凋亡细胞。结果ASODN实验组在第8天后测定最终瘤质量,与各对照组在统计学上均有显著性差异(P<0.05)。常规病理观察ASODN实验组可见肿瘤细胞生长受抑制,肿瘤组织可见片状坏死区,而且这些区域可见大量炎性细胞浸润。空白对照组、脂质体对照组、脂质体SODN对照组MVD分别为(19.57±3.37)、(21.94±4.41)、(20.49±3.91),ASODN实验组MVD为(11.30±2.79),差异显著(P<0.05)。空白对照组、脂质体对照组、脂质体SODN对照组AI分别为(3.53±1.89)、(3.86±2.14)、(4.47±2.30),ASODN实验组AI为(28.45±2.76),差异显著(P<0.05)。结论Survivin基因反义寡核苷酸可显著抑制血管内皮生长因子的表达,导致内皮细胞凋亡和毛细血管迅速退化,从而达到抑制肿瘤生长的目的。Objective To investigate the effect of antisense oligonucleotide （ASODN） against survivin on the apoptosis and vasiformation in nude mice after colorectal cancer ceils transplantation. Methods After the establishment of the xenografi model of colorectal cancer in nude mice, the 24 animals were randomized into 4 groups with 6 mice in each group, that is, control group, Lipofectamine group, Lipofectamine ＋ SODN group and Lipofectamine ＋ ASODN group. Lipofectamine, SODN or ASODN was directly injected into the corresponding xenografl in 1,4 and 8 d after tumorigenesis. The final weight of tumor mass was measured to calculate the suppression rate of tumor. The tumor tissues were morphologically observed by HE staining, the expression of survivin was measured by immunohistochemical method to calculate the microvessel density （MVD）, and the apoptosis of tumor cells was detected by TUNEL. Results There was significant difference in the final weight of tumor mass in Lipofectamine ＋ ASODN group with the other groups （ P 〈 0.05 ） , and the pathological observation showed that the growth of tumor cells was inhibited in this group. The tumor mass of this group showed necrosis in the lamellar zone and infiltration of massive inflammatory cells. The MVD of tumor was 19.57±3.37 in control group, 21.94±4.41 in Lipofectamine group, 20.49±3.91 in Lipofectamine ＋ SODN group, and 11.30±2.79 in Lipofectamine ＋ ASODN group. Significant difference was seen between Lipofectamine ＋ ASODN group with the other groups （P 〈0.05）. The apoptotic index （AI） was 3.53±1.89, 3.86±2.14, 4.47±2.30, and 28.45±2.76 respectively for above mentioned groups. There was also significant difference between Lipofectamine ＋ ASODN group with the other groups （P 〈0.05）. Conclusion Survivin ASODN inhibits significantly the expression of vascular endothelial growth factor （ VEGF）, induces the apoptosis of endothelial cells and the degeneration of capillaries, and thus suppresses the growth of tumor.

关 键 词：SURVIVIN基因 反义寡核苷酸 大肠癌模型 微血管密度 

分 类 号：R73-362[医药卫生—肿瘤] R730.23[医药卫生—临床医学]