Isopenicin A和Artemisitene的抗肿瘤活性及作用机制研究

	Isopenicin A和Artemisitene的抗肿瘤活性及作用机制研究; Anti-tumor Studies of Isopenicin A and Artemisitene
	陈琳
导师	李艳
摘要	Cancer is a serious threat to human health and has become the second cause of Cancer the human deaths all over the world. Natural products are an important source of anti-tumor drugs. The study of anti-tumor targets and mechanisms of natural products is the main content of natural product research, which can lay the foundation for the development of anti-tumor drugs. Microtubules are involved in celluar processes of movement, intracellular trafficking and mitosis, thus it is an important target for pharmaceutical research and cancer therapy. Herein, we found isopenicin A, a novel meroterpenoid isolated from the plant endophytic fungus of Penicillium sp. sh18, as a novel microtubule inhibitor with new chemotype. By studying the anti-tumor effect of isopenicin A, we found the compound evoked G2/M cell cycle arrest and subsequent cell apoptosis through effectively inhibiting the accumulation of microtubules in tumor cells, contributing to proliferation inhibition of human tumor cell lines. Our study provides an anti-tumor target and mechanism of isopenicin A and lays a foundation for discovery and development of promising microtubule inhibitors. NF-κB signaling is constitutively active in a variety of cancers and microenvironment and closely related to tumor occurrence, development and metastasis. The discovery of inhibitors targeting this signaling pathway is an important strategy for the development of anti-tumor drugs. Artemisitene (ATT) is an endoperoxide of the sesquiterpene lactone. ATT markedly inhibits the growth of cancer cells through inducing G2/M cell cycle arrest and apoptosis. The mechanism study shows that ATT inhibits the activity of NF-κB signaling pathway. Dual-luciferase reporter assay and Western Blot experiments illustrated that ATT can inhibit the transcriptional activity of NF-κB signaling pathway and the expression of downstream target genes. Furthermore, ATT inhibits the phosphorylation of IKKβ and IκBα then subsequently blocks nuclear translocation of p65. Overexpression of IKKβ reversed the effect that ATT induced cancer cell death, cell apoptosis and cell cycle arrest. Our study lays a foundation for the further development of artemisitene as an anti-tumor drug.
	2020-05
文献类型	学位论文
条目标识符	http://ir.kib.ac.cn/handle/151853/74111
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	陈琳. Isopenicin A和Artemisitene的抗肿瘤活性及作用机制研究, Anti-tumor Studies of Isopenicin A and Artemisitene[D],2020.

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