基于p53通路探索芳基喹啉的抗结肠癌活性  

Antitumor Activities of Arylquinolines aginst Colorectal Cancer Based on P53Signaling Pathway

作　　者：鲁玉凡 韩晨晨 武兴康 秦雪梅[1] LU Yufan;HAN Chenchen;WU Xingkang;QIN Xuemei(Modern Research Center for Traditional Chinese Medicine,Shanxi University,Taiyuan 030006,China)

机构地区：[1]山西大学中医药现代研究中心,山西太原030006

出　　处：《山西大学学报（自然科学版）》2022年第4期1107-1116,共10页Journal of Shanxi University(Natural Science Edition)

基　　金：山西省科技厅基础研究计划项目(201901D211141);山西省高等学校科技创新项目(2019L0094)。

摘　　要：肿瘤蛋白53(p53)是一种转录因子,调控多种类型的细胞应激响应,与肿瘤的发生发展预后密切相关,探索p53对药物刺激的响应,为抗肿瘤药物研究提供了一种思路。文章通过构建p53荧光素酶报告基因系统,以结肠癌细胞为模式细胞,建立基于p53信号通路的抗结肠癌药物筛选模型,从6-取代芳基-2-甲氧基喹啉类衍生物3a-3s中发现最优抗结肠癌化合物3i。作用机制研究显示,3i诱导DNA损伤,引起p53表达升高,诱导细胞凋亡,发挥抗肿瘤作用。此外,p53功能缺陷引起结肠癌细胞对3i的耐药性。Tumor protein 53(p53)is a transcription factor that modulates varied cell stress response signals,and is closely associated with the development and prognosis of cancer.Evaluating the response of p53 to drug stimuli provides a passway for developing antitumor drug.To open an opportunity for evaluating the response of p53 to drug stimuli,a p53 luciferase report gene system was constructed.Taking colorectal cancer(CRC)cells as model cells,a p53 signaling pathway-based anti-CRC drug screening assay model was established to make the indentification of 3i as a most efficient anti-CRC agent from 6-substituted-aryl-2-methoxyquinolines named 3a-3s.The results from the study of the action mechanisms showed that 3i exerted anti-CRC activity via the p53-mediated apoptosis through triggering DNA damage.Besides,the deficiency of p53 function lead to the drug resistance of CRC cells to 3i.

关 键 词：P53 荧光素酶报告基因 药物筛选 结肠癌 

分 类 号：O436[机械工程—光学工程]