多花蒿与暗绿蒿中抗肿瘤活性成分筛选及机制研究

	多花蒿与暗绿蒿中抗肿瘤活性成分筛选及机制研究; Discovery and mechanism study of antitumor active constituents from Artemisia myriantha and Artemisia atrovirens
	张心湉
导师	陈纪军
摘要	The discovery of novel chemical structures with anti-tumor activity and the study of their unique mechanism of action are the subjects of great concern in cancer drug research. Natural products are important sources of anti-tumor drugs, in order to discover novel anti-tumor molecules, 75 compounds isolated from Artemisia myriantha and Artemisia atrovirens were tested for their anti-hepatoma and anti-cervical cancer activities. It was found that 20 sesquiterpenes (1, 5 ~ 7, 9 ~ 13, 15, 18 ~ 20 ,24, 26, 29 ~ 32 and 36) from Artemisia myriantha inhibited HepG2 with IC50 of 4.9-35.5 μM. Especially, the IC50 of three compounds 9, 10 and 36 were 4.9, 8.6 and 7.4 μM, respectively, which was equivalent to that of sorafenib. It was also found that nine guaianolide dimers (53, 56, 58 ~ 60, 64 ~ 66 and 68) from Artemisia atrovirens inhibited HeLa S3 and SiHa cells with IC50 of 4.6-8.9 μM and 3.4-9.7 μM, respectively, which was equivalent to that of cisplatin. On the basis of activities screening, the anti-hepatoma mechanism of lavandiolide H (64) was studied. The effects of lavandiolide H (64) in migration, invasion, proliferation cycle and apoptosis were explored on HepG2. The results presented that lavandiolide H (64) inhibited cell migration and invasion, blocked cell cycle in G2/M phase by suppressing expression of cyclinB1/cdc2, and induced apoptosis by affecting Bcl-2/PARP-1 pathway on HepG2 cells. The anti-cervical cancer mechanism of artematolide A (53) was also studied. The effects of artematrolide A (53) in cell colony formation, migration, invasion, proliferation cycle, apoptosis, the level of reactive oxygen species, ERK pathway, alkaline phosphatase (ALP), thiamine, pyruvate dehydrogenase (PDC), α-ketoglutarate dehydrogenase (OGDC), the level of ATP and the production of lactate were detected on HeLa S3 and SiHa cells. The results presented that artematrolide A (53) inhibited cell colony formation, migration and invasion of HeLa S3 and SiHa cells, blocked cell cycle and induced apoptosis. Moreover, artematrolide A (53) rose intracellular ROS level, leading to increased phosphorylation of MEK1/2 and ERK1/2, decreased phosphorylation of mTOR, and inhibited expression of HIF-1α. Furthermore, artematolide A (53) suppressed the activity, transcription and translation of alkaline phosphatase (ALP), activated PDC and ODGC in mitochondria. It made mitochondrial aerobic respiration dominant in the process of cell metabolism and inhibited aerobic glycolysis. Finally, the level of ATP was increased and the production of lactate was decreased. The results indicated that artematolide A (53) inhibited cervical cancer cell proliferation by activating the ROS/ERK/mTOR pathway and promoting metabolic shift from aerobic glycolysis to mitochondrial respiration. The study is the first to found a series of anti-hepatoma and anti-cervical cancer active constituents from Artemisia myriantha and Artemisia atrovirens, and preliminarily revealed the anti-tumor mechanism
	2021-05
文献类型	学位论文
条目标识符	http://ir.kib.ac.cn/handle/151853/74525
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	张心湉. 多花蒿与暗绿蒿中抗肿瘤活性成分筛选及机制研究, Discovery and mechanism study of antitumor active constituents from Artemisia myriantha and Artemisia atrovirens[D],2021.

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