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塞来昔布在肿瘤发展中的分子机制。

The molecular mechanisms of celecoxib in tumor development.

作者信息

Wen Bin, Wei Ying-Ting, Mu Lan-Lan, Wen Guo-Rong, Zhao Kui

机构信息

Department of Gastroenterology, Affiliated Hospital to Zunyi Medical University, Zunyi, Guizhou Province, China.

出版信息

Medicine (Baltimore). 2020 Oct 2;99(40):e22544. doi: 10.1097/MD.0000000000022544.

Abstract

BACKGROUND

Clinical studies have shown that celecoxib can significantly inhibit the development of tumors, and basic experiments and in vitro experiments also provide a certain basis, but it is not clear how celecoxib inhibits tumor development in detail.

METHODS

A literature search of all major academic databases was conducted (PubMed, China National Knowledge Internet (CNKI), Wan-fang, China Science and Technology Journal Database (VIP), including the main research on the mechanisms of celecoxib on tumors.

RESULTS

Celecoxib can intervene in tumor development and reduce the formation of drug resistance through multiple molecular mechanisms.

CONCLUSION

Celecoxib mainly regulates the proliferation, migration, and invasion of tumor cells by inhibiting the cyclooxygenases-2/prostaglandin E2 signal axis and thereby inhibiting the phosphorylation of nuclear factor-κ-gene binding, Akt, signal transducer and activator of transcription and the expression of matrix metalloproteinase 2 and matrix metalloproteinase 9. Meanwhile, it was found that celecoxib could promote the apoptosis of tumor cells by enhancing mitochondrial oxidation, activating mitochondrial apoptosis process, promoting endoplasmic reticulum stress process, and autophagy. Celecoxib can also reduce the occurrence of drug resistance by increasing the sensitivity of cancer cells to chemotherapy drugs.

摘要

背景

临床研究表明塞来昔布可显著抑制肿瘤发展,基础实验和体外实验也提供了一定依据,但塞来昔布具体如何抑制肿瘤发展尚不清楚。

方法

对所有主要学术数据库(PubMed、中国知网(CNKI)、万方、维普中国科技期刊数据库(VIP))进行文献检索,包括塞来昔布对肿瘤作用机制的主要研究。

结果

塞来昔布可通过多种分子机制干预肿瘤发展并减少耐药性形成。

结论

塞来昔布主要通过抑制环氧化酶-2/前列腺素E2信号轴,从而抑制核因子-κ基因结合、Akt、信号转导子和转录激活子的磷酸化以及基质金属蛋白酶2和基质金属蛋白酶9的表达,来调节肿瘤细胞的增殖、迁移和侵袭。同时发现,塞来昔布可通过增强线粒体氧化、激活线粒体凋亡过程、促进内质网应激过程和自噬来促进肿瘤细胞凋亡。塞来昔布还可通过增加癌细胞对化疗药物的敏感性来减少耐药性的发生。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2cb5/7535670/4d32caad93c0/medi-99-e22544-g001.jpg

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