The role of nitric oxide and its interaction with cyclooxygenase in colon cancer

Abstract

<P>GSNO INHIBITED THE IN VITRO GROWTH OF THREE COLON CANCER CELL LINES WITH DIFFERENT COX-2 EXPRESSION AND ACTIVITY IN A CONCENTRATION-DEPENDENT MANNER, WHILE IT INDUCED BOTH COX-1 AND COX-2 EXPRESSION AND INCREASED PGE2 PRODUCTION. THE INHIBITION OF COX DID NOT IMPROVE THE INHIBITORY EFFECT OF GSNO ON CELL GROWTH, SUGGESTING THE EFFECT IS INDEPENDENT OF THE COX.</P><P>SEQUENTIAL DELETION ANALYSIS OF THE PROXIMAL 6.6KB COX-2 PROMOTER AND FURTHER MUTATION ANALYSIS IDENTIFIED THE BINDING SITES OF CRE AND NF-IL6 IN THE COX-2 PROMOTER AS INDISPENSABLE ELEMENTS IN BOTH THE CONSTITUTIVE AND NO-INDUCED COX-2 TRANSCRIPTION ACTIVITY IN COLON CANCER CELLS. </P><P>A SELECTIVE COX-2 INHIBITOR FURTHER ENHANCED THE CYTOKINES-INDUCED INOS PROTEIN EXPRESSION AND ACTIVITY IN HCA7, BUT THE ADDITION OF EXOGENOUS PGE2 FAILED TO REVERT IT. THE INHIBITION OF INOS INHIBITED THE COX-2 EXPRESSION AND ACTIVITY BOTH IN CONTROL AND CYTOKINE TREATED HCA7 CELLS, INDICATING A NEGATIVE FEEDBACK LOOP BETWEEN INOS AND