survivin反义寡核苷酸对人胃癌细胞裸鼠皮下移植瘤P53蛋白表达的影响

Effect of survivin antisense oligodeoxynucleotide on the expression of P53 protein in the subcutaneous transplanted tumor of human gastric carcinoma cells in nude mice

目的研究survivin反义寡核苷酸（ASODN）能否抑制人胃癌细胞皮下移植瘤生长，及与P53蛋白的关系。方法将对数生长期SGC-7901胃痛细胞种植到2只裸鼠皮下，形成母瘤，再分别种植于其他裸鼠背部皮下。成瘤后随机分为4组（survivin-ASODN＋脂质体绢、survivin—ASODN组、脂质体组、对照组，每组n=8）。瘤体内隔日给药，停药后48h处死裸鼠，剥离瘤组织，称取瘤重，计算抑瘤率。Westernblot法检测survivin的表达，免疫组化法检测各组P53蛋白的表达。结果survivin—ASODN＋脂质体组的移植瘤生长速度明显减慢，其抑瘤率为33．19％。survivin—ASODN＋脂质体组的survivin蛋白、P53蛋白表达量明显低于对照组（P〈0．05）。结论survivin—ASODN对胃癌移植瘤生长有抑制作用，能够抑制survivin蛋白的表达，亦能抑制P53蛋白的表达，P53在survivin抑制凋亡的信号通路中亦起到一定作用。

Objective To investigate the effect of antisense oligodeoxynucleotide （ASODN） targeting survivin on the inhibition of the growth of subcutaneous transplanted tumor of human gastric carcinoma ceils as well as its relationship with P53 protein. Methods Human gastric carcinoma SGC -7901 cells during the exponential phase of growth were subcutaneously implanted in two mice so as to form the parent tumor, which was subcutaneously transplanted in the other mice. The mice with tumor forn/atinn were randomized into four groups （ n = 8 each） ： surviviu - ASODN ＋ liposome group, survivin- ASODN group, liposome group and control group. Medication was administered into the tumor every other day. 48 h after drug withdrawal, the animals were sacrificed and the tumors were obtained for weight measurement and calculation of the tumor inhibition rate. The expression of smwivin and 1：53 protein in each group was determined by Western blot and immunohistoebemistry, respectively. Results The growth of transplanted tumor was markedly retarded in survivin - ASODN ＋ liposome group, at a tumor inhibitory rate of 33.19%. hnmunohistoehemistry and Western blotting indicated that the expression levels of proteins survivin and P53 protein in smwivin - ASODN ＋ liposome group were significantly lower than those in the control group （ P 〈 0.05 ）. Conclusion Survivin ASODN has inhibitory effect on the growth of the subeutaneous transplanted tumor of human gastric eells and ean inhibit the expression of protein survivin as well as P53 protein, p53 has a certain part to play in the inhibition of the apoptotic pathway by survivin.