الفهرس 
Introduction and aim of the workOnly 14 pages are availabe for public view
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Abstract
Colorectal cancer is one of the most common types of cancer in the world. Epidemiological studies have shown that non-steroidal antiinflammatory drugs reduce the risk of colorectal adenomas and carcinomas. However there are almost few data about the effect of aspirin on early stages of colorectal tumorigenesis.
Our work was to examine the effect of aspirin on pre-neoplastic lesion; aberrant crypt foci and to identify the mechanism of aspirin when used as a chemopreventive agents or a chemotherapy.
First we used 1, 2 dimethylhydrazine (DMH) for induction of ACF in rats and we divide the rats into 5 groups ; control group, DMH control group, DMH with aspirin group (as a chemopreventive), DMH then aspirin group (as a chemotherapy) and aspirin control group.
In histopathological examination we found that aspirin is able to provide 59 % decline in prevalence of ACF in aspirin treated rats. ACF was found in 88 % when aspirin given after the carcinogen indicating non-significant reduction in this group.
Also it was found that aspirin treatment resulted in a redistribution pattern of dysplastic ACF. The aspirin treated group (group B) displayed a 48 % reduction in dysplastic ACF compared with DMH control group (group A). There was no significant reduction in dysplastic ACF in group (group C).
So we found that aspirin has the ability to prevent the ACF when it is given as a chemopreventive but it can not be used as a treatment for the lesion.
Using immunohistochemistry, we examine the PCNA expression as a proliferative marker and we found that there is an increase in the expression of PCNA in group treated with the carcinogen and there is no significant reduction in the aspirin-treated groups indicating that aspirin has no effect on the proliferation of the cells and the same results obtained by the immunoblot as we examined the expression of PCNA in the nuclear extract. It is found that PCNA expression not affected in aspirin-treated rats either when given with or after the carcinogen.
To examine the mechanism of aspirin, we prepared the nuclear extract from rats colon and measured the concentration of the NF-kB by the new ELISA kit and we found that there is high significant increase of the NF-kB in the rats injected with the carcinogen. Also we found that there is significant reduction (p<0.05) in the active NF-kB in the rats consuming aspirin with the carcinogen but not in the rats taking aspirin after occurrence of the lesion suggesting that aspirin may prevent NF-kB activation.
Also based on immunoblot, we examined the expression of Bcl2 which found in the cytoplasmic extract. We found that aspirin decreased Bcl2 expression in the rats taking aspirin concomitantly with DMH and there are strong positive correlation between NF-kB concentration in the nuclear extract and Bcl-2 expression in the cytoplasmic extract suggestion that aspirin may decrease the expression of Bcl-2 (antiapoptotic gene) via inhibition of NF-kB activation.
All of these results indicate that aspirin may prevent prevalence of ACF in experimental rats but cannot cure it and we can suggest that aspirin may inhibit NF-kB activation and cause down-regulation of Bcl2 so it enhances the apoptosis of the cancer cells but it slightly affects the proliferation of these cells.
If the effects of ASA on colorectal cancer can be shown in animal models and humans, populations at risk could be targeted in future chemopreventive trials hopes of decreasing the incidence of this disease