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Cancer Chemotherapy and Pharmacology

, Volume 62, Issue 5, pp 811–819

First Online: 05 February 2008Received: 19 June 2007Accepted: 21 December 2007

Abstract

IntroductionNonsteroidal anti-inflammatory drugs NSAIDs have been shown to reduce the risk of colorectal cancer in cyclooxygenase-2 COX-2 overexpressing colorectal cancers. The present study was designed to evaluate the inhibitory effects of the COX-2 inhibitor celecoxib on the growth of colorectal cancer liver metastases in a syngeneic rat model, CC531.

Materials and methodsThe effects of celecoxib on cell viability in vitro were evaluated by treatment of CC531 tumor cell cultures with celecoxib. In vivo, Wag-Rij rats were inoculated with CC531 tumor cells at two sites in the liver and treated with celecoxib starting one week before, or directly after tumor inoculation. Control rats were inoculated without treatment. Three weeks after tumor inoculation rats were sacrificed. Tumor size, immune cell infiltration, caspase-3 activity, PGE2 and celecoxib levels were determined.

ResultsCC531 tumors did not show COX-2 expression. Tumor growth was significantly inhibited by celecoxib treatment in a dose dependent manner. Immune cell infiltration was decreased after celecoxib treatment, indicating that the immune system was not involved in preventing tumor growth. Tumor caspase-3 levels were only significantly increased if treatment was started before tumor inoculation. Celecoxib serum concentration starting at 0.84 μg-ml significantly inhibited the outgrowth of CC531 liver tumors. In contrast, in vitro concentrations of celecoxib of at least 12 μg-ml were needed to affect tumor cell viability.

ConclusionThese results suggest that the inhibitory effects of celecoxib on tumor growth are not by direct cytotoxicity, but by creating an unfavorable environment for tumor growth.

KeywordsCyclooxygenase-2 Prostaglandins Immune response CC531 rat colon tumor liver metastases model Celecoxib AbbreviationsCOX-2Cyclooxygenase-2

PGE2Prostaglandin E2

AAArachidonic acid

TCRT cell receptor

TH cellsT helper cells

NK cellsNatural Killer cells

ppmParts per million

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Autor: Pieter de Heer - Maro H. Sandel - Gunther Guertens - Gert de Boeck - Margaretha M. Koudijs - J. Fred Nagelkerke - Jan 

Fuente: https://link.springer.com/



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