摘要
目的:探讨Bcl-xl反义寡核苷酸(ASODN)对裸鼠人鼻咽癌移植瘤的生长抑制作用和机制探讨。方法:建立裸鼠人鼻咽癌模型,随机分成5组,包括生理盐水组、2.5、5.0和10.0mg/kg ASODN组,10.0mg/kg序列对照寡核苷酸组(SCODN)(每组8只)。接种肿瘤细胞后24h之内皮下注射进行治疗,透射电镜观察肿瘤大小和细胞形态变化,并用RT-PCR和蛋白质印迹法检测反义治疗后肿瘤细胞中靶基因Bcl-xl、相关凋亡基因Bcl-2、bax mRNA和蛋白表达变化。结果:2.5、5.0和10.0mg/kg ASODN对荷瘤裸鼠的抑瘤率分别为6.8%、26.4%和41.7%,呈明显的量效关系,其中10.0mg/kg ASODN通过持续局部皮下给药具有较明显的抗肿瘤作用,与对照组相比差异有统计学意义,P<0.01,并且明显下调了Bcl-xl、Bcl-2mRNA和蛋白表达水平,对bax mRNA和蛋白水平无影响。而SCODN组抑瘤率仅为19.0%,差异无统计学意义,对Bcl-xl、Bcl-2、bax mRNA和蛋白水平均无明显影响,P>0.05。结论:局部用ASODN对荷瘤裸鼠鼻咽癌的生长和基因表达具有一定的抑制作用,为鼻咽癌的治疗提供新的思路。
OBJECTIVE： To investigate the inhibitory effects of Bcl-xl antisense oligodeoxynueleotides（ASODN） on the growth and gene expression of human nasopharyngeal careinoma（NPC） in nude mice. METHODS： CNE-2Z cell line was implanted subcutaneously into the nude mice,and the mice were randomly divided in- to 5 group （n=8）. ASODN was injected subcutaneously at different doses of 2.5, 5.0 and 10.0 mg/kg, and control oligodeoxynu- cleotide （SCODN） was injected subcutaneously at a dose of 10.0 mg/kg, respectively. The morphological changes of tumor cells were observed by transmission electron micrographs, and RT-PCR and Western-blot were performed for Bcl-xl, Bcl-2 and bax gene expressions. RESULTS： The inbibitory rates of 2.5, 5.0 and 10.0 mg/kg ASODN groups were 6.8%, 26.4% and 41.7% respectively, and 19.0%was in the SCODN group. Only the inhibitory rate of 10. 0 mg/kg ASODN had a statistically significant difference compared with the control（P〈0.01）, while at the same dose there was no significant difference in the growth of SCODN treated tumors compared with the control. Bcl-xl and Bcl-2 mRNA and protein levels declined, but had no effect on gene expression of bax in the ASODN group, and SCODN also had no obvious influence on mRNA and protein levels of Bcl-xl, Bcl-2 and bax. CONCLUSIONS： Bcl xl antisense oligodexynucleotides could result in dramatic reduction of NPC growth in nude mice. It may be a novel approach to improve treatment outcome of human nasopbaryngeal carcinoma.
出处
《中华肿瘤防治杂志》
CAS
2009年第12期890-893,共4页
Chinese Journal of Cancer Prevention and Treatment
关键词
鼻咽肿瘤/病理学
寡核苷酸
反义
聚合酶链反应
小鼠
裸
nasopharyngeal neoplasms/pathology
oligonucleotides, antisense
polymerase chain reachino
mice, nude
