The Potential Role of Cyclooxygenase-2 Inhibitors in the Treatment of Experimentally-Induced Mammary Tumor

Abstract

There is an increasing body of evidence highlighting the potential antitumor activity of NSAIDs, and particularly COX-2 inhibitors. Therefore this study aimed at investigating the possible in vivo antitumor activity of the COX-2 inhibitor; celecoxib and the non-selective COX inhibitor; diclofenac, on an animal model of mammary tumor; Solid Ehrlich Carcinoma (SEC) (Osman et al., 1993), and whether the in vivo antitumor activity of celecoxib (if any) is mediated through nitric oxide (NO) release. In addition the possibility if COX inhibitors may enhance the cytotoxic activity of antitumor drags such as doxorubicin was investigated. The effects of modulating NO synthesis on the growth of SEC were also studied through the use of L-arginine (precursor of NO) and L-NAME (NOS inhibitor). Moreover, by using cultures of Ehrlich Ascites Carcinoma (EAC) cells, the probable mechanism(s) underlying the possible interaction between COX inhibitors and doxorubicin was investigated. In addition, the effects of COX inhibitors, doxorubicin as well as L-NAME and L-arginine (alone or in combination) on DNA fragmentation pattern of cultured EAC cells were also studied. To achieve these objectives the effects of different drug treatments alone or in combination on the following parameters were assessed: 1) Time-course effects of different treatments on the volume of solid Ehrlich carcinoma. 2) The delay in the growth of SEC caused by different treatments. 3) DNA content of SEC.