核受体在食管癌中的作用。

Roles of Nuclear Receptors in Esophageal Cancer.

机构信息

State Key Laboratory of Chemical Resource Engineering, College of Life Science and Technology, Beijing University of Chemical Technology, Beijing, P.R. China.

Key Laboratory of Receptors-Mediated Gene Regulation and Drug Discovery, School of Medicine, Inner Mongolia Medical University, Hohhot, Inner Mongolia, P.R. China.

出版信息

Curr Pharm Biotechnol. 2023;24(12):1489-1503. doi: 10.2174/1389201024666230202155426.

DOI:10.2174/1389201024666230202155426

PMID:36740804

Abstract

BACKGROUND

Esophageal cancer (EC), including esophageal squamous cell carcinoma (ESCC) and esophageal adenocarcinoma (EAC), is a highly prevalent malignancy that occurs predominantly in the Asian region and is related to ethnicity, genetics, diet, and lifestyle. The nuclear receptor (NR) superfamily consists of 48 members of the human body. It is a collection of a large class of transcription factors, including Peroxisome proliferator-activated receptors (PPARs), Farnesol X receptor (FXR), Vitamin D receptor (VDR), Retinoic acid receptor (RAR), Pregnane X receptor (PXR), Androgen receptor (AR) and so on. Several NRs have been detected as oncogenes or tumor suppressors in EC progression.

OBJECTIVES

NRs are associated with the progression of many cancers, including EC. Some NRs, such as PPARs and FXR, play an important role in EC. Studying the molecular mechanism of NRs in EC is helpful for further understanding the development of EC. Preclinical research and development of small molecule compound drugs targeting NRs have provided new ideas for the potential targeted therapy of EC.

METHODS

This review summarizes the studies on NRs in EC in recent years, mainly including cell experiments and animal experiments.

RESULTS

NRs influence EC progress in a variety of ways. They mainly affect the proliferation, migration and drug resistance of EC cells by affecting key cancer cell signaling pathways. Activation or inhibition of NRs inhibits or promotes EC progression, depending on EC types and tumor stages. Preclinical studies mainly focus on the development of small molecule drugs for targeting NRs (such as PPARγ agonists, PPARδ inhibitors, and FXR agonists), and agonists or inhibitors of NRs will become a potential therapeutic regimen for EC.

CONCLUSION

The studies on the roles of NRs in EC have provided a theoretical basis for us to further understand the pathogenesis of EC and develop potential therapeutic drugs targeting NRs for the treatment of different diseases.

摘要

背景

食管癌（EC），包括食管鳞状细胞癌（ESCC）和食管腺癌（EAC），是一种在亚洲地区高发的恶性肿瘤，与种族、遗传、饮食和生活方式有关。核受体（NR）超家族包括人体的 48 个成员。它是一大类转录因子的集合，包括过氧化物酶体增殖物激活受体（PPARs）、法尼醇 X 受体（FXR）、维生素 D 受体（VDR）、维甲酸受体（RAR）、孕烷 X 受体（PXR）、雄激素受体（AR）等。一些 NR 已被检测为 EC 进展的癌基因或肿瘤抑制因子。

目的

NR 与包括 EC 在内的许多癌症的进展有关。一些 NR，如 PPARs 和 FXR，在 EC 中发挥重要作用。研究 NR 在 EC 中的分子机制有助于进一步了解 EC 的发生发展。针对 NR 的小分子化合物药物的临床前研究和开发为 EC 的潜在靶向治疗提供了新的思路。

方法

本综述总结了近年来 NR 在 EC 中的研究，主要包括细胞实验和动物实验。

结果

NR 通过影响关键的癌细胞信号通路，以多种方式影响 EC 的进展。它们主要通过影响 EC 细胞的增殖、迁移和耐药性来影响 EC 进展。NR 的激活或抑制取决于 EC 类型和肿瘤分期，从而抑制或促进 EC 进展。临床前研究主要集中在针对 NR 的小分子药物的开发上（如 PPARγ 激动剂、PPARδ 抑制剂和 FXR 激动剂），NR 的激动剂或抑制剂将成为 EC 的潜在治疗方案。