title: Targeting cyclooxygenase-2 with sodium butyrate and NSAIDs on colorectal adenoma/carcinoma cells.
abstract: OBJECTIVE
  The protective effects of sodium butyrate and NSAIDs (especially the highly selective COX-2 inhibitors) have attracted considerable interest recently. In this study, primary adenoma cells and HT-29 were used to investigate whether the above drugs would be effective for reducing proliferation and inducing apoptosis. Additionally, it was investigated whether NSAIDs would strengthen the effects of sodium butyrate and its possible mechanisms.
  
  
  METHODS
  In vitro primary cell culture of colorectal adenomas and HT-29 were used for this investigation. PGE2 isolated from HT-29 cell culture supernatants was investigated by ELISA. MTT was employed to detect the anti-proliferative effects on both adenoma and HT-29 culture cells. FCM was used for apoptosis rate and cell cycle analysis. The morphology of apoptotic cells was investigated by means of electromicroscopy.
  
  
  RESULTS
  Sodium butyrate could stimulate the secretion of PGE2, while NSAIDs inhibited it to below 30 pg/10(6) cells. Both butyrate and NSAIDs could inhibit cell proliferation and induce apoptosis. The effects were time- and dose-dependent (P<0.05). Aspirin and NS-398 could enhance the effects of sodium butyrate. The effects were stronger while sodium butyrate was used in combination with NS-398 than it was used in combination with aspirin.
  
  
  CONCLUSIONS
  Butyrate and NSAIDs could inhibit cell proliferation and induce apoptosis respectively. NSAIDs could enhance the effects of sodium butyrate by down-regulating COX-2 expression. Selective COX-2 inhibitor is better than traditional NSAIDs.
authors.affiliation: Department of Gastroenterology, First Hospital, Western China University of Medical Sciences, Chengdu 610041, Sichuan Province, China. zhang-821@21cn.com
authors.forename: Zhi-Hong
authors.initials: ZH
authors.lastname: Zhang
authors.forename: Qin
authors.initials: Q
authors.lastname: Ouyang
authors.forename: Hua-Tian
authors.initials: HT
authors.lastname: Gan
mesh_terms: D000236:Adenoma / Q000473:pathology* / Q000517:prevention & control; D017209:Apoptosis / Q000187:drug effects; D002087:Butyrates / Q000494:pharmacology*; D049109:Cell Proliferation / Q000187:drug effects; D015179:Colorectal Neoplasms / Q000473:pathology* / Q000517:prevention & control; D016861:Cyclooxygenase Inhibitors / Q000494:pharmacology*; D015232:Dinoprostone / Q000378:metabolism; D019073:HT29 Cells / Q000187:drug effects; D006801:Humans; D008854:Microscopy, Electron; D009578:Nitrobenzenes / Q000494:pharmacology*; D013449:Sulfonamides / Q000494:pharmacology*; D014407:Tumor Cells, Cultured
chemical_list: D002087:Butyrates; D016861:Cyclooxygenase Inhibitors; D009578:Nitrobenzenes; D013449:Sulfonamides; C080955:N-(2-cyclohexyloxy-4-nitrophenyl)methanesulfonamide; D015232:Dinoprostone