Bcl-2反义寡核苷酸对裸鼠人肺癌移植瘤抑制作用的研究

目的探讨Bcl-2反义寡核核苷酸(ASODN)对裸鼠人肺癌移植瘤的成瘤能力和生长的抑制作用。方法将经硫代修饰的Bcl-2ASODN导入非小细胞肺癌。NCI-H460细胞内,然后将这种细胞接种于裸鼠皮下,观察肿瘤出现的时间和肿瘤体积的变化,并计算抑瘤率。同时采用未经处理的NCI-H460细胞接种于裸鼠背部皮下建立裸鼠人肺癌移植瘤模型,待长出瘤结节直径为≥5mm后,分为Bcl-2ASODN实验组、生理盐水对照组和无义寡核苷酸对照组3组。实验组用15mg/kgASODN两天一次直接瘤内注射,连用3周,测肿瘤大小变化和组织形态学改变。结果Bcl-2ASODN作用后的NCI-H460细胞在裸鼠皮下成瘤能力降低,最大抑瘤率达87.5%(P

Effect of Bcl-2 Antisense Oligodeoxynucleotides on Human Lung Carcinoma Transplanted Subcutaneously in Nude Mice

Objective: To investigate the inhibitory effects of the Bcl-2 antisense oligodeoxynucleotides (ASODN) on tumor formation and growth of human lung carcinoma transplanted subcutaneously in nude mice. Methods: Human NCI-H460 cells treated with Bcl-2 ASODN or nonesense oligodeoxynucleotide (NSODN) and untreated NCI-H460 cells were respectively implanted subcutaneously into nude mice. When the diameters of tumor were above 0.5 cm after untreated NCI-H460 cells injection, the mice bearing tumor were randomly divided into three groups: saline control group, Bcl-2 ASODN group, NSODN group. ODN was directly injected into the tumor body for 3 weeks. The weight and volume of subcutaneous tumors were measured, and the morphology of tumor cells was observed. Results: The tumorigenic ability of the treated NCI-H460 cells by Bcl-2 ASODN was reduced. The mean time at which tumor can be detected was prolonged up to 12.6 days (P<0.01). The maximum tumor growth inhibitory rate was 87.5%. In therapeutic efficacy, growth of tumor was significantly inhibited in Bcl-2 ASODN group as compared with that in NSODN group, saline-treated group (P<0.01). The NSODN control was ineffective. In comparison with NSODN-treated, saline-treated mice, those treated with Bcl-2 ASODN showed a significant decrease in median weight of subcutaneous tumors (P<0.01). The growth inhibitory rate was 71.0% in ASODN group. Conclusion: Bcl-2 ASODN could inhibit tumor formation and tumor growth in nude mice.