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World J Gastroenterol. May 28, 2007; 13(20): 2872-2877
Published online May 28, 2007. doi: 10.3748/wjg.v13.i20.2872
5-aminosalicylic acid in combination with nimesulide inhibits proliferation of colon carcinoma cells in vitro
Hai-Ming Fang, Qiao Mei, Jian-Ming Xu, Wei-Juan Ma
Hai-Ming Fang, Qiao Mei, Jian-Ming Xu, Wei-Juan Ma, Department of Gastroenterology, The First Affiliated Hospital, Anhui Medical University; The Key Laboratory of Digestive Diseases of Anhui Province, Hefei 230032, Anhui Province, China
Hai-Ming Fang, Department of pharmacology, Anhui Medical University, Hefei 230032, Anhui Province, China
Author contributions: All authors contributed equally to the work.
Supported by The Key Laboratory of Digestive Diseases of Anhui Province and colleagues from Department of Gastroenterology, The First Affiliated Hospital, Anhui Medical University, China
Correspondence to: Jian-Ming Xu, Department of Gastro-enterology, The First Affiliated Hospital, Anhui Medical University, Hefei 230032, Anhui Province, China. funhemon@163.com
Telephone: +86-551-2922039 Fax: +86-551-2922382
Received: January 27, 2007
Revised: February 3, 2007
Accepted: February 14, 2007
Published online: May 28, 2007
Abstract

AIM: To investigate the effects of 5-aminosalicylic acid (5-ASA) in combination with nimesulide on the proliferation of HT-29 colon carcinoma cells and its potential mechanisms.

METHODS: Inhibitory effects of drugs (5-ASA, nimesulide and their combination) on HT-29 colon carcinoma cells were investigated by thiazolyl blue tetrazolium bromide (MTT) assay. Cellular apoptosis and proliferation were detected by TUNEL assay and immunocytochemical staining, respectively.

RESULTS: Pretreatment with 5-ASA or nimesulide at the concentration of 10-1000 μmol/L inhibited proliferation of HT-29 colon carcinoma cells in a dose-dependent manner in vitro (t = 5.122, P < 0.05; t = 3.086, P < 0.05, respectively). The inhibition rate of HT-29 colon carcinoma cell proliferation was also increased when pretreated with 5-ASA (100 μmol/L) or nimesulide (100 μmol/L) for 12-96 h, which showed an obvious time-effect relationship (t = 6.149, P < 0.05; t = 4.159, P < 0.05, respectively). At the concentration of 10-500 μmol/L, the apoptotic rate of HT-29 colon carcinoma cells significantly increased (t = 18.156, P < 0.001; t = 19.983, P < 0.001, respectively), while expression of proliferating cell nuclear antigen (PCNA) was remarkably decreased (t = 6.828, P < 0.05; t = 14.024, P < 0.05, respectively). 5-ASA in combination with nimesulide suppressed the proliferation of HT-29 colon carcinoma cells more than either of these agents in a dose-dependent and time-dependent manner (t = 5.448, P < 0.05; t = 4.428, P < 0.05, respectively).

CONCLUSION: 5-ASA and nimesulide may inhibit the proliferation of HT-29 colon carcinoma cells and coadministration of these agents may have additional chemopreventive potential.

Keywords: Colorectal cancer, 5-aminosalicylic acid, Nimesulide