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Anticancer Res. 2006 Mar-Apr;26(2A):995-9.

PSC 833, an inhibitor of P-glycoprotein inhibits 1,2-dimethylhydrazine-induced colorectal carcinogenesis in male Fischer F344 rats.

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1
Department of Laboratory Medicine and Pathobiology, University of Toronto, Toronto, ON, Canada.

Abstract

BACKGROUND:

The expression of P-glycoprotein (Pgp) is intimately associated with cancer development. In order to explore the therapeutic value of Pgp as a target for chemotherapy, we studied the effect of PSC 833 (PSC), a potent inhibitor of Pgp, on 1,2-dimethylhydrazine (1,2-DMH)-initiated colorectal carcinogenesis in rats.

MATERIALS AND METHODS:

Male Fischer 344 rats, initiated with 1,2-DMH coupled with partial hepatectomy, were exposed to dietary 1% orotic acid for 22 weeks. They were then fed either the AIN93G basal diet (BD) or BD containing PSC (a daily dose of 15 mg/kg body weight) for 35 weeks.

RESULTS:

PSC significantly inhibited colorectal tumor multiplicity by 53% and tumor burden by 74%. PSC-mediated inhibition was evident in tumors as small as 2 mm in diameter and remained effective throughout the course of tumor growth. Histological assessment showed that PSC significantly inhibited tumor progression to colorectal adenocarcinoma by 63%.

CONCLUSION:

Collectively, this study indicates that PSC inhibited experimental colorectal carcinogenesis initiated with 1,2-DMH in rats.

PMID:
16619498
[Indexed for MEDLINE]
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