title: Meloxicam in the treatment of in vitro and in vivo models of urinary bladder cancer.
abstract: To assess the efficacy of meloxicam, a non-steroidal anti-inflammatory drug (NSAID), on three human urinary bladder-cancer cell lines (HT1376, T24 and 5637) and on mice urinary bladder cancer chemically induced by N-butyl-N-(4-hydroxybutyl) nitrosamine (BBN). The in vitro effects of meloxicam were assessed by optical microscopy, 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide (MTT) method, flow cytometry and comet assay. In vivo, Hsd:ICR male mice were exposed to BBN in drinking water, over the course of 12 weeks. Subsequently, animals were treated with meloxicam by intraperitoneal route, for 6 consecutively weeks. Tumour development was evaluated by haematoxylin and eosin staining. Renal and hepatic functions, interleucin-6 (IL-6), C-reactive protein (CRP) and tumour necrosis factor (TNFα) were also evaluated. In vitro, meloxicam induced a significant (P<0.05) decrease of cell proliferation. A significant (P<0.05) cell cycle arrest on G0/G1 phase was also detected in all the cell lines, with a slight but significant increase of sub-G0/G1 fraction on T24 (P=0.006) and 5637 (P<0.001) cells. Also a significant (P<0.05) increase in DNA damage was found on meloxicam-treated cells. In vivo, the incidence of pre-neoplastic lesions induced by BBN was not affected by meloxicam treatment. However, although not statistically significant, the development of neoplastic lesions was inhibited by meloxicam treatment without significant alterations of renal or hepatic parameters. Meloxicam is effective on in vitro and in vivo models of urinary bladder cancer. These findings support that meloxicam deserves more attention on urinary bladder cancer study.
authors.affiliation: Department of Veterinary Sciences, CECAV, University of Trás-os-Montes and Alto Douro, Vila Real, Portugal.
authors.forename: Regina
authors.initials: R
authors.lastname: Arantes-Rodrigues
authors.forename: Rosário
authors.initials: R
authors.lastname: Pinto-Leite
authors.forename: Rita
authors.initials: R
authors.lastname: Ferreira
authors.forename: Maria João
authors.initials: MJ
authors.lastname: Neuparth
authors.forename: Maria João
authors.initials: MJ
authors.lastname: Pires
authors.forename: Isabel
authors.initials: I
authors.lastname: Gaivão
authors.forename: Carlos
authors.initials: C
authors.lastname: Palmeira
authors.forename: Lúcio
authors.initials: L
authors.lastname: Santos
authors.forename: Aura
authors.initials: A
authors.lastname: Colaço
authors.forename: Paula
authors.initials: P
authors.lastname: Oliveira
mesh_terms: D000818:Animals; D000970:Antineoplastic Agents / Q000008:administration & dosage / Q000494:pharmacology*; D002085:Butylhydroxybutylnitrosamine / Q000633:toxicity; D059447:Cell Cycle Checkpoints / Q000187:drug effects; D049109:Cell Proliferation / Q000187:drug effects; D020552:Comet Assay; D016861:Cyclooxygenase Inhibitors / Q000008:administration & dosage / Q000494:pharmacology*; D004249:DNA Damage / Q000187:drug effects; D005434:Flow Cytometry; D006801:Humans; D007274:Injections, Intraperitoneal; D008297:Male; D000077239:Meloxicam; D051379:Mice; D008813:Mice, Inbred ICR; D008853:Microscopy / Q000379:methods; D009374:Neoplasms, Experimental / Q000188:drug therapy / Q000473:pathology; D011230:Precancerous Conditions / Q000188:drug therapy / Q000473:pathology; D013843:Thiazines / Q000008:administration & dosage / Q000494:pharmacology*; D013844:Thiazoles / Q000008:administration & dosage / Q000494:pharmacology*; D001749:Urinary Bladder Neoplasms / Q000188:drug therapy* / Q000473:pathology
chemical_list: D000970:Antineoplastic Agents; D016861:Cyclooxygenase Inhibitors; D013843:Thiazines; D013844:Thiazoles; D002085:Butylhydroxybutylnitrosamine; D000077239:Meloxicam