Anti-inflammatory drugs such as NSAIDS inhibit the formation of prostaglandins, particularly PGE2. There are several isoforms of the enzyme directly responsible for the formation of PGE2, and one of these, mPGES-1 (microsomal prostaglandin E synthase-1) is an inducible enzyme. Thus, the expression of mPGES-1 is increased in inflamed tissues, and this increased expression correlates with an increase in COX-2. To see if this enzyme represents a possible target of drugs, bone cancer pain was evaluated in mPGES-1 knockout mice.
mPGES-1 KO mice exhibited a delay in exhibiting pain related behaviors as well as a decrease in the size of the tumor, relative to wild type mice. Levels of PGE2 were markedly reduced in mPGES-1 KO mice as well as the level of another pro-nociceptive molecule, CGRP. Wild type mice given celecoxib had similar levels of pain related behaviors and bone loss as mPGES-1 KO mice.
This suggests that inhibition of inflammatory molecules, particularly PGE2, may help reduce bone cancer related pain and the progression of the tumor. mPGES-1 may be a suitable target for drug development because it may reduce pain and inflammation, while avoiding the side effects associated with both selective and non-selective COX inhibitors.
http://www.ncbi.nlm.nih.gov/pubmed/21324324
SBrookshire495K
This is a very interesting article! I mean we keep seeing how these COX inhibitors are useful in treatment but as you mentioned, there are side effects of selective and non-selective COX inhibitors. I think mPGES-1 seems like a promising target for drugs and would be interesting to see more research on this enzyme. In particular, one of the uses i was thinking of as i read the your post was its possible use for those who suffer from osteoporosis. Perhaps if mPGES-1 targeting can help reduce bone loss it would be a good ideas to look into how effective this can be in minimizing bone loss in those with osteoporosis or other diseases leading to bone loss.
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