Comparing the effects of COX and non-COX-inhibiting NSAIDs on enhancement of apoptosis and inhibition of aberrant crypt foci formation in a rat colorectal cancer model
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Date
2013
Authors
Martin, Jonathan Edward
Young, Graeme Paul
Le Leu, Richard Kevin
Hu, Ying
Journal Title
Journal ISSN
Volume Title
Publisher
International Institute of Anticancer Research
Rights
Rights Holder
International Institute of Anticancer Research
Abstract
The protection against colorectal cancer (CRC)
by non-steroidal anti-inflammatory drugs (NSAIDs) is in part
dependent on inhibition of cyclooxygenase (COX). We
compared the efficacy of the non-COX-inhibiting R
flurbiprofen (R-FB) with COX-inhibiting sulindac and
racemic flurbiprofen (Rac-FB), and determined their effects
on apoptosis, in an azoxymethane (AOM)-induced rat CRC
model. In experiment 1, groups of rats were given daily drug
gavage (R-FB 30 mg/kg, Rac-FB 10 mg/kg and Sulindac 20
mg/kg) for one week, followed by AOM treatment and were
killed eight hours later, colons were examined for apoptosis
and cell proliferation. In experiment 2, groups of rats were
given two AOM treatments, followed by daily drug gavage
until they were killed ten weeks later, colons were examined
for aberrant crypt foci (ACF) and prostaglandin E 2
production. All drugs significantly enhanced apoptosis and
inhibited ACF, irrespective of their COX-inhibiting potency
(p<0.01), but sulindac was more potent in inhibition of large
ACF, p<0.05. COX-inhibiting sulindac achieved the greatest
protective effect. The greater safety profile of Rac-FB should
provide an advantage for chemoprevention.
Description
Keywords
Colorectal cancer, Cancer research
Citation
Martin, J.E., Young, G.P., Le Leu, R.K. and Hu, Y., 2013. Comparing the effects of COX and non-COX-inhibiting NSAIDs on enhancement of apoptosis and inhibition of aberrant crypt foci formation in a rat colorectal cancer model. Anticancer Research, 33, Accepted for publication 17 July 2013.