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Immunohistochemical expression of P‐glycoprotein in the rat urinary bladder and the effect of verapamil on intravesical chemotherapy
Author(s) -
Hashimoto Hiroshi,
Tokumitsu Masayuki,
Saga Yuji,
Okuyama Mitsuhiko,
Yachiku Sunao
Publication year - 2001
Publication title -
international journal of urology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.172
H-Index - 67
eISSN - 1442-2042
pISSN - 0919-8172
DOI - 10.1046/j.1442-2042.2001.00263.x
Subject(s) - verapamil , pirarubicin , medicine , p glycoprotein , chemotherapy , immunohistochemistry , urinary system , urinary bladder , multiple drug resistance , efflux , intracellular , urology , pathology , pharmacology , drug resistance , biology , calcium , genetics , microbiology and biotechnology
Background: The expression of P‐glycoprotein (Pgp) is thought to be common in bladder epithelium and the multidrug resistance mediated by Pgp must be considered to improve the efficacy of chemotherapy for bladder tumors. Methods: The expression of Pgp in normal and tumor tissue of the rat urinary bladder was first examined immunohistochemically. The effect of verapamil, an expected modulator of Pgp, on intravesical chemotherapy of the rats was then investigated. Results: Pgp was immunohistochemically detected in normal epithelium and in tumor tissue of the rat urinary bladder. In those normal and tumor‐bearing bladders, verapamil promoted the uptake of intravesically instilled pirarubicin, but the efflux of intracellular accumulated pirarubicin was observed subsequently in both conditions with and without verapamil. The drug concentration decreased more rapidly in the verapamil group than in the control group. Conclusions: Verapamil is thought to be useful in promoting uptake of intravesically instilled pirarubicin, but it did not appear to be so efficient at limiting the efflux of intracellular accumulated pirarubicin.