Author/Authors :
Jalali, Amir Toxicology Research Center - Department of Pharmacology and Toxicology - Faculty of Pharmacy - Ahvaz Jundishapur University of Medical Sciences , Ghasemian, Sepideh Toxicology Research Center - Department of Pharmacology and Toxicology - Faculty of Pharmacy - Ahvaz Jundishapur University of Medical Sciences , Najafzadeh, Hossein Department of Pharmacology - Faculty of Veterinary Medicine - Shahid Chamran University , Galehdari, Hamid Department of Genetic - Faculty of Sciences - Shahid Chamran University , Seifi, Masoud Reza Department of Virology - Faculty of Veterinary Medicine - Shahid Chamran University , Zangene, Fateme Department of Pharmacology and Toxicology - Faculty of Pharmacy - Shahid Beheshti University of Medical Sciences , Dehdardargahi, Shaiesteh School of Medicine - Arvand Medical Science University - International Branch of Jundishapur University of Medical Sciences
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.
Keywords :
P-Glycoprotein , Hepatocellular Carcinoma , Rifampin , Verapamil , Marla Gene
