靶向端粒酶催化亚单位基因hEST2反义寡核苷酸对人肝癌细胞生长的抑制作用.DOCVIP

临床医学论文-靶向端粒酶催化亚单位基因hEST2反义寡核苷酸对人肝癌细胞生长的抑制作用 ????????? 作者：杨波 脱朝伟 张宁 刘秋珍 王明耀?? 【摘要】? 目的 观察靶向端粒酶催化亚单位基因hEST2反义寡核苷酸对人肝癌细胞生长的抑制作用。方法 从Genebank中钓取人端粒酶催化亚单位基因hEST2的mRNA序列，通过计算机模建二级结构辅助设计并合成硫化修饰反义寡核苷酸(癌泰得)。采用人肝癌裸小鼠原位移植模型(HCMY89)。实验分为生理盐水组，5FU 10 mg/kg组，癌泰得50 mg/kg组、75 mg/kg组，癌泰得75 mg/kg联合5FU 10 mg/kg组、50 mg/kg联合5FU 10 mg/kg组。尾静脉给药，每天1次，连续20 d。观察移植瘤质量和抑瘤率、移植瘤体积、AFP浓度和移植瘤组织学。结果 (1)5FU 10 mg/kg组的抑瘤率为27.85%，其他各治疗组的抑瘤率均在42.14%～74.29%之间；(2)各治疗组瘤质量、瘤体积和AFP浓度均低于生理盐水组且差异有统计学意义；(3)瘤体积和AFP浓度之间呈直线关系，为显著正相关(r=0.997 7)；(4)癌泰得和5FU治疗人肝细胞癌后，肝癌细胞出现不同程度的凋亡、坏死，同时伴有纤维组织增生。结论 癌泰得对肝癌细胞生长具有抑制作用，疗效优于5FU；与5FU合用具有协同抗肿瘤效应。 【关键词】? 端粒酶催化亚单位；反义寡核苷酸；原发性肝细胞癌；原位移植；裸小鼠；疾病模型 　　Inhibitory effect of antisense oligodeoxynucleotide targeted against telomerase catalytic subunit gene hEST2 on the growth of human hepatocellular carcinoma cells? ??? 【Abstract】? Objective? To investigate the inhibitory effect of antisense oligodeoxynucleotide targeted against telomerase catalytic subunit gene hEST2 on the growth of hepatocellular carcinoma (HCC) cells. Methods? mRNA sequence of hEST2 was obtained from Genebank database. Computer was applied in helping imitate the secondary structure of mRNA and design antisense oligodeoxynucleotide. Chemosynthesis method was used to synthesize the sulfurized antisense oligodeoxynucleotide targeted against hEST2 (Cantide). Orthotopic implantation model of hepatocellular carcinoma in nude mice (HCMY89) was established. All mice were divided into normal saline group (negative control), 5FU 10 mg/kg group (positive control), Cantide 50 mg/kg group, Cantide 75 mg/kg group, Cantide 75 mg/kg plus 5FU 10 mg/kg group, Cantide 50 mg/kg plus 5FU 10 mg/kg group. Vena caudalis injection was done on all mice once per day for 20 days continuously to observe weight, volume, histology and inhibition rate of implanted tumors, AFP concentration. Results? (1) Inhibition rate of tumor was 27.85% in 5FU 10 mg/kg group but 42.14%74.29% in other groups. (2) In the treatment group, the tumor h