title: PC-407, a celecoxib derivative, inhibited the growth of colorectal tumor in vitro and in vivo.
abstract: This study aimed to observe the growth-inhibitory effect of PC-407 (4-[5-naphthyl-3-(trifluoromethyl)-1H-pyrazol-1-yl] benzenesulfonamide), a celecoxib derivative synthesized in our lab, in human colorectal cancer cells and a colitis-associated colorectal cancer (CACC) model, and investigate the relative molecular mechanisms. SW-1116 (expressing a high level of cyclooxygenase-2 [COX-2]), HT-29 (expressing a moderate level of COX-2), and SW-480 (no expression of COX-2) cell lines were exposed to different concentrations of celecoxib (0-100 micromol/L) or PC-407 (0-100 micromol/L). Then, COX-2 levels were assessed by reverse transcription-PCR and Western blotting. COX-2 activity was evaluated by measuring prostaglandin E(2) concentration using enzyme-linked immunoassay. A mouse model of colitis-associated carcinogenesis was employed to determine the effect of PC-407 in vivo. PC-407 inhibited cell growth in a concentration-dependent manner, and the IC(50) values of PC-407 for growth inhibition of SW-1116, HT-29, and SW-480 cells were 17.60 +/- 3.02, 18.14 +/- 2.81, and 8.13 +/- 0.40 micromol/L, respectively. PC-407 down-regulated COX-2 mRNA and protein levels and reduced prostaglandin E(2) production significantly. In vivo, PC-407 inhibited the genesis of CACC effectively. Our data indicate that PC-407 can inhibit the growth of tumor both in vitro and in vivo and suggest that the effect probably involves inhibition of the COX-2 pathway and other COX-2-independent pathways.
authors.affiliation: Department of Pharmacology, School of Pharmacy, the Fourth Military Medical University, Shaanxi, China.
authors.forename: Yuhua
authors.initials: Y
authors.lastname: Li
authors.forename: Yinbo
authors.initials: Y
authors.lastname: Niu
authors.forename: Huanjie
authors.initials: H
authors.lastname: Wu
authors.forename: Bangle
authors.initials: B
authors.lastname: Zhang
authors.forename: Yang
authors.initials: Y
authors.lastname: Sun
authors.forename: Haitao
authors.initials: H
authors.lastname: Huang
authors.forename: Qian
authors.initials: Q
authors.lastname: Li
authors.forename: Lei
authors.initials: L
authors.lastname: Fan
authors.forename: Li
authors.initials: L
authors.lastname: Liu
authors.forename: Qibing
authors.initials: Q
authors.lastname: Mei
mesh_terms: D000818:Animals; D000970:Antineoplastic Agents / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects; D000068579:Celecoxib; D045744:Cell Line, Tumor; D015179:Colorectal Neoplasms / Q000188:drug therapy* / Q000473:pathology; D052246:Cyclooxygenase 2 Inhibitors / Q000494:pharmacology; D019073:HT29 Cells; D006801:Humans; D008297:Male; D051379:Mice; D008813:Mice, Inbred ICR; D009281:Naphthalenes / Q000494:pharmacology*; D010766:Phosphorylation; D011720:Pyrazoles / Q000494:pharmacology; D013449:Sulfonamides / Q000494:pharmacology*; D051176:beta Catenin / Q000378:metabolism; D000096926:Benzenesulfonamides
chemical_list: D000970:Antineoplastic Agents; D000068579:Celecoxib; D052246:Cyclooxygenase 2 Inhibitors; D009281:Naphthalenes; D011720:Pyrazoles; D013449:Sulfonamides; D051176:beta Catenin; C497664:4-(5-naphthyl-3- (trifluoromethyl)-1H-pyrazol-1-yl)benzenesulfonamide; D000096926:Benzenesulfonamides