| Budget Amount *help |
¥2,400,000 (Direct Cost: ¥2,400,000)
Fiscal Year 1997: ¥600,000 (Direct Cost: ¥600,000)
Fiscal Year 1996: ¥900,000 (Direct Cost: ¥900,000)
Fiscal Year 1995: ¥900,000 (Direct Cost: ¥900,000)
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| Research Abstract |
In this study, we examined the mRNA expression of phospholipase A2 and cyclooxygenase (COX)-2 on arachidonic acid cascade in rat colon carcinogenesis. Those expressions in carcinomas were significantly increased, and those in colon mucosa exposed with carcinogen were also induced. In addition, we examined the effects of NS-398, which is a selective COX-2 inhibitor, on the development of aberrant crypt foci (ACF), which is a pre-neoplastic lesion in rat colon carcinogenesis. As the results, NS-398 inhibited the formation of ACF.Now the long-term experiment for the chemoprevention of NS-398 is going on.
[Methods] We used azoxymethane (AOM)-induced colon carcinogenesis model to examine the effect of NS-398,10mg/kg. And the expressions of COX-1 and -2, and cell proiferative potential were examined.
[Results & Discussion] While the number of ACF in rats treated with AOM alone was 0.97(]SY.+-。[)0.32, that is rats treated with AOM and NS-398 (0.42(]SY.+-。[)0.14) was significantly decreased (P<0.001). The expressions of COX-1 and 2 in both groups treated with or without NS-398 were not significantly different. However, the cell proliferative potential in rats treated with NS-398 was decreased compared with that without NS-398. According to the results, COX inhibitors, which are related to the arachidonic acid cascade and non-steroid anti-inflammatory drugs (NAIDs), are considered the chemopreventive agents. Furthermore, as it has been reported that NSAIDs have potentials of apoptosis induction, the apoptotic mechanism of the inhibitory effect of NS-398 in colon carcinogenesis should be examined in future.
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