5-aminosalicylic acid in combination with nimesulide inhibits proliferation of colon carcinoma cells in vitro.
OBJECTIVE
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 micromol/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 micromol/L) or nimesulide (100 micromol/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 micromol/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).


CONCLUSIONS
5-ASA and nimesulide may inhibit the proliferation of HT-29 colon carcinoma cells and coadministration of these agents may have additional chemopreventive potential.
Fang
Hai-Ming
HM
Department of Gastroenterology, The First Affiliated Hospital, Anhui Medical University, Hefei 230032, Anhui Province, China.
Mei
Qiao
Q
Xu
Jian-Ming
JM
Ma
Wei-Juan
WJ
D000230:Adenocarcinoma / Q000188:drug therapy / Q000473:pathology*; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000494:pharmacology* / Q000627:therapeutic use; D017209:Apoptosis / Q000187:drug effects; D049109:Cell Proliferation / Q000187:drug effects*; D003110:Colonic Neoplasms / Q000188:drug therapy / Q000473:pathology*; D016861:Cyclooxygenase Inhibitors / Q000494:pharmacology* / Q000627:therapeutic use; D004305:Dose-Response Relationship, Drug; D004359:Drug Therapy, Combination; D019073:HT29 Cells; D006801:Humans; D019804:Mesalamine / Q000494:pharmacology* / Q000627:therapeutic use; D013449:Sulfonamides / Q000494:pharmacology* / Q000627:therapeutic use
D000894:Anti-Inflammatory Agents, Non-Steroidal; D016861:Cyclooxygenase Inhibitors; D013449:Sulfonamides; D019804:Mesalamine; C012655:nimesulide