Amlodipine (P-glycoprotein inhibitor) modulation Doxorubicin Immunohistochemical effect in induced CRC in Mice

Abstract

A trial was conducted to assess the P-gp inhibitor Amlodipine (AML) in induced colorectal cancer (CRC) in mice by Azoxymethane (AOX) treated with Doxorubicin (DXO) alone or combined with AML. Forty-eight adult Albino mice were equally divided to six groups consisting of C-ve given NS and five groups treated after CRC induction according to the dosing regimen: C-ve (AOX 10 mg/kg and NS), T1 (AML 1.8 mg/kg), T2 (DOX 5 mg/kg), T3 (AML 1.8 mg/kg with DOX 2.5 mg/kg) and T4 (AML 1.8 mg/kg with DOX 5 mg/kg). Dosing continued for four weeks, followed by two weeks recovery through which clinical, physiological and proliferating cell nuclear antigen (PCNA) parameters were evaluated. Clinical observation showed slightly weakness in all treated animal groups with abnormal clinical symptoms and recorded a noticeable appearance of swelling masses in the tail and partial alopecia especially in the C+ve group. Also, the results showed there was a significant decrease in animal body weight after CRC induction by AOM, while at the second week of recovery body weight recorded a significant increase in the T3 and T4 groups while a significant decrease in animal body weight in the T2 and control positive groups at the end of the experiment. The findings score of PCNA showed a therapeutic effect on CRC-induced mice within the two periods of experiment in the treated groups T1, T3, and T4 except the T2 group in comparison with the C+ve group. The results recorded a significance decrease in PCNA-LI score in T3, T4, and T1 respectively in comparison with the C+ve group with an improved anti-colorectal cancer effect recorded in T3 combined therapy according to the result of least PCNA level than other treated groups.