Effect of the specific cyclooxygenase-2 inhibitor meloxicam on tumour growth and cachexia in a murine model

The effects of the cyclooxygenase-2 (COX-2) inhibitor, meloxicam, on tumour growth and cachexia have been determined in 2 established murine adenocarc inomas (MAC). At a dose level of 2.5 and 5.0 mgkg(-1), meloxicam produced p ronounced inhibition of the growth of the MAC13 tumour, increasing the tumo ur volume doubling time from 2 to 5 days. Meloxicam also suppressed growth of the MAC16 tumour, which is generally refractory to standard cytotoxic ag ents, increasing the tumour volume doubling time from 1.5 to 2.5 days at do se levels of 0.5 and 1.0 mgkg(-1). Cachexia was also effectively attenuated at these dose levels. To investigate whether meloxicam exerted a direct ef fect on the cachectic process, studies on protein degradation were carried out using C2C12 mouse myoblasts in response to a proteolysis-inducing facto r (PIF). PIF produced maximum protein degradation at a concentration of 4.2 nM, and this was effectively attenuated by meloxicam at concentrations gre ater than 1 mu M. This suggests that meloxicam may be capable of directly a ntagonizing the process of muscle catabolism in cachexia. Int. J. Cancer 87 :95-100, 2000. (C) 2000 Wiley-Liss, Inc.