title: [Celecoxib increased cellular ATRA sensitivity of human colon cancer cell lines through COX-2-independent mechanisms].
abstract: Retinoid resistance has limited clinical activity of retinoids as differentiation-inducing and apoptosis-inducing drugs. The present study was designed to investigate whether celecoxib (selective COX-2 inhibitor) has effects on cellular retinoid sensitivity of human colon cancer cell lines and its possible mechanism. Cell viability was measured by MTT assay. Apoptosis was detected by Annexin-V/PI staining and flow cytometry assay. PGE2 production was measured by ELISA assay. Expression of RARbeta was assayed by Western blotting. The results showed that celecoxib enhanced the inhibitory effect of ATRA in both COX-2 high-expressing HT-29 and COX-2 low-expressing SW480 cell lines. Further study showed the ATRA and celecoxib combination induced greater apoptosis, and the addition of PGE2 did not affect the number of apoptotic cells induced by the combination. Moreover, NS398 (another selective COX-2 inhibitor) did not affect the inhibitory effects of ATRA on both cell lines. Western blotting showed that the expression of RARbeta in HT-29 cell lines increased in celecoxib group and combination group. And the addition of PGE2 did not affect the expression of RARbeta induced by celecoxib either. In conclusion, celecoxib increased expression of RARbeta and cellular ATRA sensitivity through COX-2-independent mechanisms, which may provide a potential strategy for combination therapy.
authors.affiliation: The Third Affiliated Hospital of Sun Yat-sen University, Guangzhou 510630, China.
authors.forename: Jian-Pei
authors.initials: JP
authors.lastname: Liu
authors.forename: Hong-Bo
authors.initials: HB
authors.lastname: Wei
authors.forename: Zong-Heng
authors.initials: ZH
authors.lastname: Zheng
authors.forename: Wei-Ping
authors.initials: WP
authors.lastname: Guo
authors.forename: Jia-Feng
authors.initials: JF
authors.lastname: Fang
mesh_terms: D000970:Antineoplastic Agents / Q000494:pharmacology; D017209:Apoptosis / Q000187:drug effects; D000068579:Celecoxib; D045744:Cell Line, Tumor; D002470:Cell Survival / Q000187:drug effects; D003110:Colonic Neoplasms / Q000378:metabolism / Q000473:pathology*; D051546:Cyclooxygenase 2 / Q000378:metabolism*; D052246:Cyclooxygenase 2 Inhibitors / Q000494:pharmacology*; D015232:Dinoprostone / Q000378:metabolism; D004357:Drug Synergism; D019073:HT29 Cells; D006801:Humans; D009578:Nitrobenzenes / Q000494:pharmacology; D011720:Pyrazoles / Q000494:pharmacology*; D018168:Receptors, Retinoic Acid / Q000378:metabolism; D013449:Sulfonamides / Q000494:pharmacology*; D014212:Tretinoin / Q000494:pharmacology*
chemical_list: D000970:Antineoplastic Agents; D052246:Cyclooxygenase 2 Inhibitors; D009578:Nitrobenzenes; D011720:Pyrazoles; D018168:Receptors, Retinoic Acid; D013449:Sulfonamides; C082925:retinoic acid receptor beta; C080955:N-(2-cyclohexyloxy-4-nitrophenyl)methanesulfonamide; D014212:Tretinoin; D051546:Cyclooxygenase 2; C496540:PTGS2 protein, human; D000068579:Celecoxib; D015232:Dinoprostone