文献类型：期刊文献

中文题名：秀丽隐杆线虫作为Ras/MAPK信号通路的抗肿瘤药物筛选模型研究

英文题名：Using Caenorhabditis elegans is to study the antitumor drug screening model of the Ras/MAPK signaling pathway

作者：刘东玲[1,2,3];支德娟[1];白彦丽[2];周婷[2];李红玉[1]

第一作者：刘东玲

机构：[1]兰州大学药学院,甘肃兰州730000;[2]甘肃中医药大学药学院,甘肃兰州730000;[3]甘肃省中药药理与毒理重点实验室,甘肃兰州730000

第一机构：兰州大学药学院,甘肃兰州730000

年份：2018

卷号：35

期号：2

起止页码：1

中文期刊名：甘肃中医药大学学报

外文期刊名：Journal of Gansu University of Chinese Medicine

基金：国家自然科学基金青年基金项目(81603407);国家自然科学基金地区基金项目(81760789);甘肃省中药药理与毒理重点实验室开放基金项目[ZDSYS-ZZKJ-2013(C)-001]

语种：中文

中文关键词：秀丽隐杆线虫;Ras/有丝分裂原蛋白活化酶(MAPK)信号通路;抗肿瘤;药物筛选模型

外文关键词：C. elgans;Ras/MAPK signal pathway;anticancer;drug screening model

摘要：目的采用秀丽隐杆线虫Ras/有丝分裂原蛋白活化酶(MAPK)信号通路上的过度激活系列突变体研究该模式生物作为Ras/MAPK信号通路的抗肿瘤药物筛选模型的可行性及其分子机制。方法采用96孔板将索拉菲尼和依托泊苷作用于L1期秀丽隐杆线虫(每孔80~100条),并设空白对照,每个处理设3个重复。培养秀丽隐杆线虫4~5 d后,于倒置生物显微镜下观察秀丽隐杆线虫野生型和突变体数目。与空白对照比较,野生型比例越高,说明药物效果越好。结果索拉菲尼能够剂量依赖性地逆转let-60/ras(gf)和mek/erk(gf)双突变体多阴门表型,对其下游转录因子lin-1(lf)和lin-31(gf)多阴门突变体几乎没有影响;依托泊苷对信号通路上游因子let-60/ras(gf)及下游转录因子突变体lin-31(gf)均有明显的抑制作用,不依赖细胞信号通路。结论秀丽隐杆线虫模型不但能够筛选靶向Ras/MAPK信号通路的抑制剂,还能评价肿瘤细胞毒药物。
Objective To study the biological model and the molecular mechanism of anti-tumor drug scree- ning model of using caenorhabditis elegans （C. elegansis） as Ras/MAPK signaling pathway using its over-activated series of mutants. Methods Sorafenib and etoposide were used to treat L1 nematodes in 96-well plate （ 80 to 100 cells per well） and a blank control group was set. Every processing method was set up with 3 replicates. After 4 to 5 days of nematode culture, the numbers of wild type and mutants of nematodes were observed under an inverted mi- croscope. Compared with the blank control,the higher wild-type ratio means the better drug efficacy. Results So- rafenib reversed the multiple vulval phenotypes of let-60/ras （gf） and raek/erk （gf） double mutants in a dose- dependent manner,but had no effects on lin-1 （lf） and lin-31 （gf） which are its downstream transcription factors. Whereas etoposide has a significant inhibitory effect on the upstream signaling factor let-60/ras （gf） and the down- stream transcription factor mutant lin-31 （gf）and does not depend on cellular signaling pathways. Conclusion C. elegans can not only screen for the inhibitors of target Ras/MAPK pathway, but also evaluate the cytotoxie drugs.