title: An apple oligogalactan potentiates the growth inhibitory effect of celecoxib on colorectal cancer.
abstract: Multiple studies have indicated that selective cyclooxygenase-2 (COX-2) inhibitors possess clinically chemopreventive and preclinically anticancer activities. Their long-term use, however, may be limited by the cardiovascular toxicity. This study tried to investigate whether an apple oligogalactan (AOG) could enhance the growth inhibitory effect of celecoxib on colorectal cancer. Caco-2 and HT-29 cell lines were exposed to different concentrations of AOG (0-1 g/L), celecoxib (0-25 μmol/L), and their combination. COX-2 levels were assessed by reverse transcription PCR and Western blot. COX-2 activity was evaluated by measuring prostaglandin E2 concentration. A colitis-associated colorectal cancer (CACC) mouse model was used to determine the effect of the combination in vivo. AOG (0.1-0.5 g/L) could potentiate the inhibitory effect of physiologic doses of celecoxib (5 μmol/L) on cell growth and decrease COX-2 expressions both at RNA and protein levels. In vivo, the combination (2.5% AOG plus 0.04% celecoxib, w/w) prevented against CACC in mice effectively. Our data indicate that AOG could potentiate the growth inhibitory effect of celecoxib on colorectal cancer both in vitro and in vivo through influencing the expression and function of COX-2 and phosphorylation of MAPKs, which suggests a new possible combinatorial strategy in colorectal cancer therapy.
authors.affiliation: a No. 422 Hospital of PLA , Guangdong , P. R. China.
authors.forename: Yuhua
authors.initials: Y
authors.lastname: Li
authors.forename: Yinbo
authors.initials: Y
authors.lastname: Niu
authors.forename: Yang
authors.initials: Y
authors.lastname: Sun
authors.forename: Lin
authors.initials: L
authors.lastname: Mei
authors.forename: Bangle
authors.initials: B
authors.lastname: Zhang
authors.forename: Qian
authors.initials: Q
authors.lastname: Li
authors.forename: Li
authors.initials: L
authors.lastname: Liu
authors.forename: Rong
authors.initials: R
authors.lastname: Zhang
authors.forename: Jianfa
authors.initials: J
authors.lastname: Chen
authors.forename: Qibing
authors.initials: Q
authors.lastname: Mei
mesh_terms: D000818:Animals; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000494:pharmacology; D018938:Caco-2 Cells; D000068579:Celecoxib; D049109:Cell Proliferation / Q000187:drug effects; D002470:Cell Survival; D003092:Colitis / Q000150:complications / Q000188:drug therapy; D015179:Colorectal Neoplasms / Q000150:complications / Q000188:drug therapy*; D051546:Cyclooxygenase 2 / Q000235:genetics / Q000378:metabolism; D015536:Down-Regulation; D005685:Galactans / Q000494:pharmacology*; D019073:HT29 Cells; D006801:Humans; D008297:Male; D027845:Malus / Q000737:chemistry*; D051379:Mice; D008813:Mice, Inbred ICR; D011720:Pyrazoles / Q000494:pharmacology*; D013449:Sulfonamides / Q000494:pharmacology*
chemical_list: D005685:Galactans; D011720:Pyrazoles; D013449:Sulfonamides; D051546:Cyclooxygenase 2; C496540:PTGS2 protein, human; D000068579:Celecoxib