青蒿素-4-芳氨基喹唑啉衍生物体外抗肿瘤机制研究

	青蒿素-4-芳氨基喹唑啉衍生物体外抗肿瘤机制研究; Study on the anti-tumor mechanism of artemisinin-4- arylaminoquinazoline derivatives in vitro
	范东梅
导师	李艳
摘要	Colorectal cancer (CRC) is one of the most common tumors in the world and the main cause of cancer death. According to the molecular mechanism of the occurrence and development of CRC, the design and development of new targeted drugs is of great significance for improving the clinical efficacy of CRC patients. Epidermal growth factor receptor (EGFR) is a receptor tyrosine kinase whose gene mutation or overexpression will activate the downstream RAS/RAF/MEK/ERK/MAPK and AKT/PI3K/mTOR signaling pathways to promote the occurrence and development of cancer. Gefitinib, as an EGFR receptor inhibitor, is a clinically used treatment for colon cancer. However, when colorectal cancer originates from the right side (Right colorectal cancer, RCC), and RAS/RAF mutations or other drug resistance of EGFR occur , Gefitinib loses its original clinical utility. Dihydroartemisinin (DHA) can exert anti-tumor effects by inducing tumor cell apoptosis, cycle arrest, angiogenesis inhibition and other mechanisms, but its activity is weak. In order to develop new and effective potential drugs for the treatment of colorectal cancer, the research group was based on the anti-tumor activity of artemisinin and the EGFR tyrosine kinase inhibitory activity of gefitinib, combined with computer-aided drug design, and used molecular hybridization technology to transform the active structure of the Artemisinin (ART) and its derivatives such as Dihydroartemisinin (DHA), Artesunate (Artesunate, AS) and the key pharmacophore of gefitinib 4- (aryl) Amino) quinazoline has synthesized a series of hybrid derivatives, and reported for the first time a novel artemisinin-4-arylamino-quinazoline hybrid molecule 32 with significant colorectal cancer inhibitory activity. In this study, using two colorectal cancer cell lines SW480, HCT116 and normal colon cell NCM460 as experimental models, we further investigated the colorectal cancer inhibitory activity of compound 32 and explored its anti-tumor mechanism. The main experimental methods used include MTS to detect in vitro tumor growth activity, EGFR Kinase Enzyme System and ADP-GloTM kinase detection kit to determine the in vitro EGFR inhibitory activity of compound 32, PI single-stained cells to detect cycle distribution, and Annexin V-FITC/PI double staining Apoptosis analysis and Western blotting。 In summary, this thesis mainly studies the superiority of the anti-tumor activity of the new artemisinin derivative 32 and its anti-tumor mechanism, in order to provide experimental evidence for the development of clinical treatment drugs for colorectal cancer. The results of the study show that, compared with the parent compound, compound 32 exhibits stronger colorectal cancer inhibitory activity by inducing cell cycle arrest and apoptosis, and compound 32 is more likely to inhibit colorectal cancer cells than normal colon cells, its anti-tumor activity in vitro is related to EGFR activity and its downstream signaling pathway inhibition and iron.
	2021-05
文献类型	学位论文
条目标识符	http://ir.kib.ac.cn/handle/151853/74576
专题	昆明植物所硕博研究生毕业学位论文
推荐引用方式 GB/T 7714	范东梅. 青蒿素-4-芳氨基喹唑啉衍生物体外抗肿瘤机制研究, Study on the anti-tumor mechanism of artemisinin-4- arylaminoquinazoline derivatives in vitro[D],2021.

条目包含的文件
文件名称/大小	文献类型	版本类型	开放类型	使用许可
范东梅-范东梅硕士毕业论文0601175（3635KB）	学位论文		限制开放	CC BY-NC-SA	请求全文