利用HDAC向的烯酸衍生物,以获得联合的抗癌和肝保护作用
Zhicheng Gu1, Mingzhenglong Deng1, Qinggen Luo1
1State Key Laboratory of Functions and Applications of Medicinal Plants, Engineering Research Center for the Development and Application of Ethnic Medicine and TCM (Ministry of Education), Guizhou Provincial Key Laboratory of Pharmaceutics, School of Pharmacy, Guizhou Medical University, Guiyang 550004, China.
研究人员开发了一种新型化合物,2c,来自醇酸 (OA),它既具有抗瘤作用,也具有肝脏保护作用. 这种化合物在提高化疗疗效的同时减少肝损伤方面显示出有前途,为抗癌和药物诱导的肝毒性提供了一种新的策略.
科学领域:
- 药用化学 医学化学
- 药理学 药理学是指药理学的学科.
- 肝病学 肝病学是一种肝病学.
背景情况:
- 开发具有肝保护性质的抗瘤药物对于双重作用的癌症治疗和缓解化疗诱导的肝损伤至关重要.
- 类酸 (OA) 是一种天然化合物,以其肝脏保护作用而闻名.
- 将肝脏保护和抗瘤活性结合在一个单一的药物中提供了显著的治疗优势.
研究的目的:
- 合成和评估由酸 (OA) 衍生的新型化合物,具有双重抗瘤和肝脏保护作用.
- 研究这些化合物的潜力,提高化疗疗效,同时减少肝损伤.
- 确定一种化合物,用于开发抗癌和药物诱导的肝毒性新策略.
主要方法:
- 通过在28-COOH位点内加入向HDAC的药,对油酸 (OA) 进行修改.
- 在体外对各种癌细胞系 (RS4;11,K562,RPMI8226,HepG2) 和正常肝细胞的抗增殖和细胞毒性作用的评估.
- 在体内评估使用HepG2异种移植模型和动物中西斯胺诱导的肝损伤模型.
- 涉及诱导亡,细胞周期分析和激活NRF2/HO-1通路的机制研究.
主要成果:
- 化合物2c对RS4;11,K562和RPMI8226细胞表现出显著的抗增殖活性,对HepG2肝癌细胞表现出细胞毒性.
- 化合物2c对正常的肝细胞表现出有利的选择性,诱导了亡,并在HepG2细胞中引起G2细胞周期停止.
- 化合物2c通过激活NRF2/HO-1通路来减轻西斯胺诱导的肝细胞和动物肝损伤,抑制体内瘤生长,并增强西斯胺的抗瘤功效,同时最大限度地降低肝毒性.
结论:
- 化合物2c是一种新型OA衍生物,具有显著的抗瘤和肝脏保护性质.
- 化合物2c为癌症治疗提供了有前途的治疗策略,提高了疗效,减少了化疗引起的肝损伤.
- NRF2/HO-1通路的激活是化合物2c的肝保护作用的关键机制.
更多相关视频
09:03Establishment of Hepatocarcinoma in BALB/c-nu Mice and Investigation of the Therapeutic Effect of the Sanleng Jiashen Formula
Published on: January 26, 2024
00:06An Oncogenic Hepatocyte-Induced Orthotopic Mouse Model of Hepatocellular Cancer Arising in the Setting of Hepatic Inflammation and Fibrosis
Published on: September 12, 2019
相关概念视频
Targeted Cancer Therapies
There are several types of targeted therapies against...
Drugs that Stabilize Microtubules
Cancer Therapies
However, cancer treatments can pose several challenges, as therapies used to kill cancer cells are generally also toxic to normal cells. Moreover, cancer cells mutate rapidly and can develop resistance to chemical agents or radiation therapy. Besides, all types of cancer cells may not respond to the same therapy. Some cancer cells respond to one...
Targets for Drug Action: Overview
Receptors are either membrane-spanning or intracellular proteins, which upon binding a ligand, get activated and transmit the signal downstream to elicit a response. Drugs bind receptors, either mimicking the action of endogenous ligands or blocking the receptor activity to bring about a modified response. Nearly 35% of approved drugs target the G...
Lipid-Lowering Drugs: Statins and Miscellaneous Agents
Acid Suppressive Drugs for Peptic Ulcer Disease: Histamine H2-Receptor Antagonists
