C-myc反义寡核苷酸联合5-FU对胃癌荷瘤裸鼠的抑瘤作用的研究  

Research of c-myc antisense oligonucleotide combined with 5-fluorouracil on growth suppression of transplanted human gastric cancer in nude mice.

作　　者：苏河[1] 蔡辉[1] 郭天康[1] 马云涛[1] 李振军[1] 

机构地区：[1]甘肃省人民医院普外科,甘肃兰州730000

出　　处：《四川医学》2007年第9期964-967,共4页Sichuan Medical Journal

基　　金：甘肃省中青年科技基金(3YS061-A25-025)

摘　　要：目的探讨C-myc反义寡核苷酸(ASODN)联合5-FU对胃癌荷瘤裸鼠的抑瘤作用。方法将30只裸鼠建立人胃癌MKN-45细胞移植瘤动物模型。成瘤后动物随机平均分为6组,分别由皮下瘤体内注射脂质体(lipofectin,Lip)、正义寡核苷酸(SODN/Lip)、反义寡核苷酸(ASODN/Lip)、5-FU、5-FU+SODN/Lip和5-FU+ASODN/Lip,每周1次,共3次。观察肿瘤抑制率、肿瘤体积和动物存活情况。RT-PCR及免疫组化法检测各组肿瘤的c-myc蛋白表达情况。结果ASODN/Lip组和5-FU组肿瘤体积明显减少,肿瘤生长抑制,抑瘤率达41.5%和36.8%,5-FU+C-mycASOND/Lip组抑制作用更为显著,抑瘤率达46.7%;ASODN/Lip组裸鼠生存期较SODN/Lip组和Lip对照组延长明显(P<0.05);RT-PCR及免疫组化显示ASODN和5-FU均使C-myc mRNA和蛋白表达下降。结论C-myc基因反义寡核苷酸联合5-FU可以有效抑制人胃癌裸鼠皮下肿瘤的生长,延长动物生存期,下调C-myc基因表达,为胃癌的治疗提供新的思路。Objective To explore the suppression effect of c-myc antisense oligonucleotide combined with 5-fluorouracil on transplanted human gastric cancer in nude mice. Methods 30 nude mice were transplanted with human gastric cancer MKN 45 cells to construct tumor models, which were divided into 6 groups（5 mice per group） ： lipofectin, SODN/Lip, ASODN/Lip, 5-FU, 5-FU ＋ SODN/ Lip and 5-FU ＋ ASODN/Lip were injected into the tumor respectively. A total of 3 injections were given, once every a week. Observations were made on tumor suppression rate,tumor volume and the survival time of the anlmals.The expression of C-myc gene in the 6 groups were detected by the method of immunohistochemistry staining and RT-PCR on the mRNA and protein level. Results Compared to control group the tumor volume decreased obviously and the rate of tumor suppression reached 41.5% and 36.8% in the group of ASODN/ Lip and 5-FU, and in the group of ASODN/Lip combined with 5-FU the rate of tumor suppression reached 46.7%. Longer survival time was observed in the group of ASODN/Lip and ASODN/Lip combined with 5-FU of nude mice compared with control anlmals.The result of immunohistochemical and RT-PCR assays showed that C-myc ASODN and 5-FU could decrease the expression of C-myc gene. Conclusion C-myc antisense oligonucleotide combined with 5-fluomuracil can effectively suppress the growth rate on gastric cancer ceils in subcutaneous tumor, prolong the survival time human of nude mice and down-regulate C-myc gene expression. It can provide a new way to treat the gastric carcinoma.

关 键 词：胃肿瘤 C-MYC反义寡核苷酸 5-氟尿嘧啶 基因治疗 

分 类 号：R735.2[医药卫生—肿瘤]