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齐墩果酸及其衍生物的抗癌活性:研究进展、靶点分析及作用机制。

Anticancer activity of oleanolic acid and its derivatives: Recent advances in evidence, target profiling and mechanisms of action.

机构信息

Department of Orthodontics, School of Stomatology, Jilin University, 1500 Qinghua Road, Changchun 130021, Jilin, PR China.

Pharmacology Department, Dalian Medical University, Dalian, Liaoning 116044, PR China.

出版信息

Biomed Pharmacother. 2022 Jan;145:112397. doi: 10.1016/j.biopha.2021.112397. Epub 2021 Nov 16.

Abstract

Oleanolic acid (OA, 3 β - hydroxyoleanolic acid-12-en-28-oic acid) is a pentacyclic triterpenoid present in many plants. As a new framework for development of semi synthetic triterpenoids, OA is of great significance in the discovery of anticancer drugs. Some of these derivatives, such as CDDO (2-cyano-3,12-dioxooleana-1, 9 (11)-dien-28-oic acid) have been verified in clinical trials, while other derivatives studied previously, such as SZC014, SZC015 and SZC017 (OA derivatives respectively), are also candidate drugs for cancer treatment. This paper reviews the preclinical studies, literature evidence, target analysis and anticancer mechanism of OA and its derivatives. The mechanism of action of its derivatives mainly includes anti-cancer cell proliferation, inducing tumor cell apoptosis, inducing autophagy, regulating cell cycle regulatory proteins, inhibiting vascular endothelial growth, anti angiogenesis, inhibiting tumor cell migration and invasion. In recent years, the molecular mechanism of OA and its derivatives has been elucidated. These effects seem to be mediated by the alterations in a variety of signaling pathways induced by OA and its derivatives. In conclusion, OA and its derivatives are considered as important candidate drugs for the treatment of cancer, indicating that OA and its derivatives have the potential to be used as anticancer drugs in practice.

摘要

齐墩果酸(OA,3β-羟基齐墩果酸-12-烯-28-酸)是一种存在于许多植物中的五环三萜。作为半合成三萜类化合物开发的新骨架,OA 在抗癌药物的发现中具有重要意义。其中一些衍生物,如 CDDO(2-氰基-3,12-二氧代齐墩果烷-1,9(11)-二烯-28-酸)已在临床试验中得到验证,而之前研究过的其他衍生物,如 SZC014、SZC015 和 SZC017(分别是 OA 的衍生物),也是癌症治疗的候选药物。本文综述了 OA 及其衍生物的临床前研究、文献证据、靶标分析和抗癌机制。其衍生物的作用机制主要包括抑制癌细胞增殖、诱导肿瘤细胞凋亡、诱导自噬、调节细胞周期调控蛋白、抑制血管内皮生长、抗血管生成、抑制肿瘤细胞迁移和侵袭。近年来,OA 及其衍生物的分子机制已被阐明。这些作用似乎是由 OA 及其衍生物诱导的各种信号通路的改变介导的。总之,OA 及其衍生物被认为是治疗癌症的重要候选药物,表明 OA 及其衍生物具有在实践中作为抗癌药物的潜力。

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