Insights into the critical role of the PXR in preventing carcinogenesis and chemotherapeutic drug resistance.

Niu, Xiaxia; Wu, Ting; Li, Gege; Gu, Xinsheng; Tian, Yanan; Cui, Hongmei

Niu, Xiaxia; Wu, Ting; Li, Gege; Gu, Xinsheng; Tian, Yanan; Cui, Hongmei.

Afiliación

Niu X; Institute of Toxicology, School of Public Health, Lanzhou University, 730000, Lanzhou, China.
Wu T; Institute of Toxicology, School of Public Health, Lanzhou University, 730000, Lanzhou, China.
Li G; Institute of Toxicology, School of Public Health, Lanzhou University, 730000, Lanzhou, China.
Gu X; Department of Pharmacology, College of Basic Medical Sciences, Hubei University of Medicine, Shiyan 442000, Hubei, China.
Tian Y; Department of Veterinary Physiology and Pharmacology, Texas A&M University, USA.
Cui H; Institute of Toxicology, School of Public Health, Lanzhou University, 730000, Lanzhou, China.

Int J Biol Sci ; 18(2): 742-759, 2022.

Article en En | MEDLINE | ID: mdl-35002522

RESUMEN

Pregnane x receptor (PXR) as a nuclear receptor is well-established in drug metabolism, however, it has pleiotropic functions in regulating inflammatory responses, glucose metabolism, and protects normal cells against carcinogenesis. Most studies focus on its transcriptional regulation, however, PXR can regulate gene expression at the translational level. Emerging evidences have shown that PXR has a broad protein-protein interaction network, by which is implicated in the cross signaling pathways. Furthermore, the interactions between PXR and some critical proteins (e.g., p53, Tip60, p300/CBP-associated factor) in DNA damage pathway highlight its potential roles in this field. A thorough understanding of how PXR maintains genome stability and prevents carcinogenesis will help clinical diagnosis and finally benefit patients. Meanwhile, due to the regulation of CYP450 enzymes CYP3A4 and multidrug resistance protein 1 (MDR1), PXR contributes to chemotherapeutic drug resistance. It is worthy of note that the co-factor of PXR such as RXRα, also has contributions to this process, which makes the PXR-mediated drug resistance more complicated. Although single nucleotide polymorphisms (SNPs) vary between individuals, the amino acid substitution on exon of PXR finally affects PXR transcriptional activity. In this review, we have summarized the updated mechanisms that PXR protects the human body against carcinogenesis, and major contributions of PXR with its co-factors have made on multidrug resistance. Furthermore, we have also reviewed the current promising antagonist and their clinic applications in reversing chemoresistance. We believe our review will bring insight into PXR-targeted cancer therapy, enlighten the future study direction, and provide substantial evidence for the clinic in future.

Asunto(s)

Carcinogénesis/genética; Resistencia a Antineoplásicos/genética; Neoplasias/prevención & control; Receptor de la Señal 1 de Direccionamiento al Peroxisoma/genética; Miembro 1 de la Subfamilia B de Casetes de Unión a ATP/genética; Animales; Citocromo P-450 CYP3A/genética; Sistema Enzimático del Citocromo P-450/genética; Regulación de la Expresión Génica; Humanos; Neoplasias/tratamiento farmacológico

Palabras clave

Pregnane nuclear receptor (PXR); chemotherapeutic drug resistance; post-translational modifications; protein-protein interactions

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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Resistencia a Antineoplásicos / Carcinogénesis / Receptor de la Señal 1 de Direccionamiento al Peroxisoma / Neoplasias Límite: Animals / Humans Idioma: En Revista: Int J Biol Sci Asunto de la revista: BIOLOGIA Año: 2022 Tipo del documento: Article País de afiliación: China Pais de publicación: Australia

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