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 adenocarcinomas (MAC). At a dose level of 2.5 and 5.0 mgkg(-1), meloxicam produced pronounced inhibition of the growth of the MAC13 tumour, increasing the tumour volume doubling time from 2 to 5 days. Meloxicam also suppressed growth of the MAC16 tumour, which is generally refractory to standard cytotoxic agents, increasing the tumour volume doubling time from 1.5 to 2.5 days at dose 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 effect on the cachectic process, studies on protein degradation were carried out using C(2)C(12) mouse myoblasts in response to a proteolysis-inducing factor (PIF). PIF produced maximum protein degradation at a concentration of 4.2 nM, and this was effectively attenuated by meloxicam at concentrations greater than 1 microM. This suggests that meloxicam may be capable of directly antagonizing the process of muscle catabolism in cachexia.
Hussey
H J
HJ
Pharmaceutical Sciences Research Institute, Aston University, UK.
Tisdale
M J
MJ
D000230:Adenocarcinoma / Q000188:drug therapy*; D000818:Animals; D001835:Body Weight / Q000187:drug effects; D002100:Cachexia / Q000188:drug therapy*; D003110:Colonic Neoplasms / Q000188:drug therapy*; D051546:Cyclooxygenase 2; D052246:Cyclooxygenase 2 Inhibitors; D016861:Cyclooxygenase Inhibitors / Q000627:therapeutic use*; D004305:Dose-Response Relationship, Drug; D007527:Isoenzymes / Q000037:antagonists & inhibitors* / Q000494:pharmacology*; D008297:Male; D000077239:Meloxicam; D051379:Mice; D008815:Mice, Inbred Strains; D009368:Neoplasm Transplantation; D011451:Prostaglandin-Endoperoxide Synthases / Q000494:pharmacology*; D013843:Thiazines / Q000627:therapeutic use*; D013844:Thiazoles / Q000627:therapeutic use*; D013997:Time Factors
D052246:Cyclooxygenase 2 Inhibitors; D016861:Cyclooxygenase Inhibitors; D007527:Isoenzymes; D013843:Thiazines; D013844:Thiazoles; D051546:Cyclooxygenase 2; D011451:Prostaglandin-Endoperoxide Synthases; D000077239:Meloxicam