维拉帕米和利福平对肝细胞癌中P-糖蛋白表达的影响。

Verapamil and rifampin effect on p-glycoprotein expression in hepatocellular carcinoma.

作者信息

Jalali Amir, Ghasemian Sepideh, Najafzadeh Hossein, Galehdari Hamid, Seifi Masoud Reza, Zangene Fateme, Dehdardargahi Shaiesteh

机构信息

Toxicology Research Center, Department of Pharmacology and Toxicology, Faculty of Pharmacy, Ahvaz Jundishapur University of Medical Sciences, Ahvaz, IR Iran.

Department of Pharmacology, Faculty of Veterinary Medicine, Shahid Chamran University, Ahvaz, IR Iran.

出版信息

Jundishapur J Nat Pharm Prod. 2014 Oct 10;9(4):e17741. doi: 10.17795/jjnpp-17741. eCollection 2014 Nov.

DOI:10.17795/jjnpp-17741

PMID:25625052

原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC4302401/

Abstract

BACKGROUND

High expression of p-glycoprotein (P-gp) has been associated with a poor prognosis in patients with hepatocellular carcinoma (HCC). It is likely that P-gp overexpression is responsible for multidrug resistance in HCC.

OBJECTIVES

The aim of this study was to elucidate the effect of potent carcinogen nitrosamine with and without verapamil and rifampin drugs on P-gp expression at the mRNA level in HCC.

MATERIALS AND METHODS

Four groups of rats (n = 5) were selected with different treatments and one group as control. mRNA concentration changes were monitored using quantitative PCR (QPCR).

RESULTS

A significant difference was found between verapamil treated group and the control regarding the mRNA level. The mdr1a mRNA was significantly decreased in the verapamil group (P ≤ 0.001). Rifampin administrated group had a decreased level of the mdr1a mRNA compared to the control group (P ≤ 0.006). No significant changes were observed in HCC induced rats regarding the mdr1a mRNA level when treated with verapamil and rifampin. An enhanced expression of the mdr1a gene was found In the HCC induced animals when treated with drugs.

CONCLUSIONS

Verapamil and rifampin were found specific and effective against P-gp expression in HCC. In conclusion, treatment efficacy of most anticancer drugs is increased in combination with verapamil and rifampin against most advanced HCC.

摘要

背景

P-糖蛋白（P-gp）的高表达与肝细胞癌（HCC）患者的不良预后相关。P-gp过表达很可能是导致HCC多药耐药的原因。

目的

本研究旨在阐明强效致癌物亚硝胺分别联合维拉帕米和利福平药物对HCC中P-gp mRNA水平表达的影响。

材料与方法

选取四组大鼠（每组n = 5）进行不同处理，一组作为对照。使用定量聚合酶链反应（QPCR）监测mRNA浓度变化。

结果

维拉帕米处理组与对照组在mRNA水平上存在显著差异。维拉帕米组中mdr1a mRNA显著降低（P≤0.001）。与对照组相比，利福平给药组的mdr1a mRNA水平降低（P≤0.006）。在用维拉帕米和利福平处理的HCC诱导大鼠中，mdr1a mRNA水平未观察到显著变化。在用药物处理的HCC诱导动物中发现mdr1a基因表达增强。