Modulation by verapamil of doxorubicin induced expression of multidrug resistance gene (mdr-1p-glycoprotein) in murine tumor cells
Joint Authors
Uthman, Abd al-Munim M.
Abd al-Wahhab, Abd al-Hadi A.
Sayyid-Ahmad, Muhammad M.
Muhammad, Muhammad A.
Source
Journal of the Egyptian National Cancer Institute
Issue
Vol. 12, Issue 3 (30 Sep. 2000), pp.221-227, 7 p.
Publisher
Cairo University National Cancer Institute
Publication Date
2000-09-30
Country of Publication
Egypt
No. of Pages
7
Main Subjects
Topics
Abstract EN
Overexpression of the transmembrane drug efflux pump p-glycoprotein (p-gp) is one of the major mechanisms by which cancer cells develop multidrug resistance (MDR) against natural product anticancer drugs including Doxorubicin (DOX).
In this study, the effects of DOX And / or DOX plus the calcium channel blocker, Verapamil, on mdr-1 / p-gp expression in Ehrlich ascites carcinoma cells (EAC-cells) were studied using Rhodamine 123 (RD 123), Western blotting and Reverse Transcriptase- Polymerase Chain Reaction (RT-PCR).
Tumor-bearing mice treated with DOX (2 mg / kg I.P.
every other day for a total of 3 doses) showed 34.1 days median survival time with 20 % long-term survivors.
However, pretreatment with Verapamil (20 mg / kg I.P.
daily for 5 days), before DOX increased the long-term survivors to 60 % with median survival time of 44.4 days.
Verapamil pretreatment increased the cellular levels of DOX at all time points tested with maximum level appeared at 6 hours after treatment (5.5 μg / 108 cells compared to 3.4 μg / 108 for DOX alone).
The expression of mdr-1 / p-gp was significantly increased 6 hours after treatment with DOX.
Verapamil pretreatment (20 mg / kg) for 5 days before DOX significantly decreased mdr-1 / p-gp expression and decreased p-gp function from 37 % to 16 %.
On the basis of our findings we may conclude : (1) DOX induced mdr-1 / p-gp expression in sensitive EAC-cells at both transcriptional and translational levels at only 6 hours post treatment.
(2) Verapamil block DOX-induced mdr-1 / p-gp expression with the consequent increase in DOX cellular uptake and cytotoxicity.
(3) Verapamil can potentiate the cytotoxic activity of DOX against the growth of EAC cells by mdr-1/p-gp independent mechanism.
American Psychological Association (APA)
Uthman, Abd al-Munim M.& Muhammad, Muhammad A.& Abd al-Wahhab, Abd al-Hadi A.& Sayyid-Ahmad, Muhammad M.. 2000. Modulation by verapamil of doxorubicin induced expression of multidrug resistance gene (mdr-1p-glycoprotein) in murine tumor cells. Journal of the Egyptian National Cancer Institute،Vol. 12, no. 3, pp.221-227.
https://search.emarefa.net/detail/BIM-69514
Modern Language Association (MLA)
Uthman, Abd al-Munim M.…[et al.]. Modulation by verapamil of doxorubicin induced expression of multidrug resistance gene (mdr-1p-glycoprotein) in murine tumor cells. Journal of the Egyptian National Cancer Institute Vol. 12, no. 3 (Sep. 2000), pp.221-227.
https://search.emarefa.net/detail/BIM-69514
American Medical Association (AMA)
Uthman, Abd al-Munim M.& Muhammad, Muhammad A.& Abd al-Wahhab, Abd al-Hadi A.& Sayyid-Ahmad, Muhammad M.. Modulation by verapamil of doxorubicin induced expression of multidrug resistance gene (mdr-1p-glycoprotein) in murine tumor cells. Journal of the Egyptian National Cancer Institute. 2000. Vol. 12, no. 3, pp.221-227.
https://search.emarefa.net/detail/BIM-69514
Data Type
Journal Articles
Language
English
Notes
Includes bibliographical references : p. 226-227
Record ID
BIM-69514