甲基巴多酮对人肝癌HepG2细胞细胞色素P450和ABC转运蛋白基因表达的影响。

IF 1.7 Q3 PHARMACOLOGY & PHARMACY

Drug Research Pub Date : 2023-10-01 Epub Date: 2023-08-17 DOI:10.1055/a-2111-6649

Katsuhito Nagai, Shuhei Fukuno, Takeshi Miura, Eri Yasuda-Imanishi, Hiroki Konishi

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引用次数: 0

摘要

甲基巴多酮（BX）有望成为一种创新的慢性肾脏疾病（CKD）治疗剂。本研究的目的是检测细胞色素P450（CYP）和ABC转运蛋白亚型在人肝癌HepG2细胞中的表达是否因暴露于BX而改变。在相同条件下，HepG2细胞暴露于BX后，CYP1A2、CYP2E1、P-糖蛋白、多药耐药相关蛋白1-3和乳腺癌症耐药蛋白的mRNA表达显著增加，而CYP3A4mRNA的表达显著降低。BX对HepG2细胞中CYP2C9和CYP2C19的mRNA表达没有显著影响。总之，本研究表明，当暴露于BX时，HepG2细胞中几种CYP和ABC转运蛋白的基因表达发生了改变，这表明需要仔细关注接受BX治疗CKD患者的药物相互作用。

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Altered Gene Expression of Cytochrome P450 and ABC Transporter in Human Hepatocellular Carcinoma HepG2 Cells Exposed to Bardoxolone Methyl.

Abstract Bardoxolone methyl (BX) is expected to be an innovate therapeutic agent for chronic kidney disease (CKD). The aim of the present study was to examine whether the expression of subtypes of cytochrome P450 (CYP) and ABC transporters was altered in human hepatocellular carcinoma HepG2 cells by exposure to BX. The expression of mRNAs for CYP1A2, CYP2E1, P-glycoprotein, multidrug resistance-associated protein 1–3, and breast cancer resistance protein was significantly increased by exposure of HepG2 cells to BX, while the expression of CYP3A4 mRNA was significantly decreased under the same conditions. BX had no significant effect on the expression of mRNAs for CYP2C9 and CYP2C19 in HepG2 cells. In conclusion, this study demonstrated that the gene expression of several CYPs and ABC transporters in HepG2 cells was altered when exposed to BX, suggesting the need to pay careful attention to drug-drug interactions in patients receiving BX for CKD treatment.

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来源期刊

Drug Research PHARMACOLOGY & PHARMACY-

CiteScore

3.50

自引率

0.00%

发文量

期刊介绍： Drug Research (formerly Arzneimittelforschung) is an international peer-reviewed journal with expedited processing times presenting the very latest research results related to novel and established drug molecules and the evaluation of new drug development. A key focus of the publication is translational medicine and the application of biological discoveries in the development of drugs for use in the clinical environment. Articles and experimental data from across the field of drug research address not only the issue of drug discovery, but also the mathematical and statistical methods for evaluating results from industrial investigations and clinical trials. Publishing twelve times a year, Drug Research includes original research articles as well as reviews, commentaries and short communications in the following areas: analytics applied to clinical trials chemistry and biochemistry clinical and experimental pharmacology drug interactions efficacy testing pharmacodynamics pharmacokinetics teratology toxicology.