端粒酶正义及反义寡核苷酸对鼻咽癌细胞生长分化的影响  

Effects of Telomerase Sense and Antisense Oligodeoxynucleotides on Growth and Differentiation of Nasop haryngeal Carcinoma Cells

作　　者：张素珍[1] 黄培春[1] 徐永[2] 陈锦[1] 蔡康荣[3] 

机构地区：[1]广东医学院病理生理学教研室,广东湛江524023 [2]广东医学院生理学教研室,广东湛江524023 [3]广东医学院分析中心,广东湛江524023

出　　处：《癌症》2002年第5期493-497,共5页Chinese Journal of Cancer

摘　　要：背景与目的:近年研究表明,端粒及端粒酶与肿瘤发生密切相关。端粒酶反义寡核苷酸直接作用于端粒酶或诱导肿瘤细胞分化均可使端粒酶活性下降,抑制肿瘤生长。而用端粒酶反义寡核苷酸直接抑制端粒酶活性是否可引起肿瘤细胞再分化,尚不清楚。由于端粒DNA重复序列是以端粒酶RNA为模板合成的,因此端粒DNA可以和端粒酶正义寡核苷酸互补结合。这种结合是否也能影响肿瘤细胞的生长,值得研究。本研究正是要探讨端粒酶正义及反义寡核苷酸对鼻咽癌细胞生长分化的作用。方法:脂质体介导正、反义寡核苷酸转染鼻咽癌CNE1和CNE2Z细胞株,MTT法检测细胞增殖能力,免疫组化法检测细胞角蛋白表达,同时观察细胞形态学变化。结果:端粒酶正义寡核苷酸与反义寡核苷酸一样可抑制CNE1和CNE2Z细胞的生长,且呈剂量和时间依赖性。1.5、3.0、4.5、6.0μmol/L正义寡核苷酸处理CNE1细胞,6h抑制率分别为16.28%、19.38%、22.48%和23.26%,48h分别达26.26%、38.89%、39.90%和38.89%;CNE2Z细胞6h抑制率分别为7.69%、8.24%、18.13%和20.32%,48h分别为28.84%、28.88%、32.89%和31.54%。正、反义寡核苷酸组细胞角蛋白表达显著增加(P<0.01),细胞形态趋向分化成熟。结论:端粒酶正、反义寡核苷酸均可抑制鼻咽癌细胞的生长,并促进细胞分化。Background &Objective:It was reported that telomere and telomerase were associated with the development of cancers.Telomerase antisense oligodeoxynucleotides(ASODN)directly act on telomerase,or induce tumor cells to differentiate,result in te lomerase activity decreases,and cells growth inhibited.However,whether the inhibition of telomerase activity by ASODN could i nduce tumor cells to differentiate i s still unknow.Telomerase RNA acts a s a template for synthesis of telomere,so telome rase sense oligodeoxynucleotides(SODN)can be hybridized to the telomere DNA.Whether this reaction could affect the growt h of tumor cells is worth being studie d.This research was just to investig ate the effects of telomerase SODN and ASODN on the grow th and differentiation of nasophary ngeal carcinoma (NPC)cells.Methods:After transfecting telomerase SODN and ASODN into NPC CNE1and CNE2Z cells by li pofectin,the proliferation of the c ells was identified by MTT method,and the exp ression of keratin was detected by immunohistochemistry.Meanwhile,the morphological changes of the cells were observed.Results:SODN inhibited the growth of CNE1and CNE2Z cells as well as ASODN in dose-and time-dependent manner.After being treated with 1.5μmol /L, 4943.0μmol /L,4.5μmol /L,and 6.0μmol /L SODN,the inhibition rates in C NE1cells for 6h were 16.28%,19.38%,22.48%,and 23.26%,respectively;f or 48h were 26.26%,38.89%,39.90%,a nd 38.89%,respectively;the inhibition rates in CNE2Z cells for 6h were 7.69%,8.24%,18.13%,and 20.32%,respectively,and for 48h were28.84%,28.88%,32.89%,and 31.54%,respectively.The keratin expressions in cells of SODN and ASODN groups were significently increased and th e cells tended to be mature.Conclusion:The telomerase SODN and ASODN could b oth inhibit the growth of NPC cells and in duce cells to differentiate.

关 键 词：鼻咽肿瘤 反义寡核苷酸 正义寡核苷酸 端粒酶 端粒 细胞生长分化 

分 类 号：R739.63[医药卫生—肿瘤]