Effect of 5-Aminosalicylic Acid on Cell Proliferation,Apoptosis and Cell Cycle in Human Colon Cancer Cell Line HT-29 / 胃肠病学

ABSTRACT

Background:Ulcerative colitis-associated colorectal cancer(UcCRC)is the most serious complication of ulcerative colitis(UC). 5-Aminosalicylic acid(5-ASA)could reduce the risk of UC progressing to UcCRC. Aims:To investigate the effect of 5-ASA on cell proliferation,apoptosis and cell cycle in human colon cancer cell line HT-29 for verifying the inhibitory effect of 5-ASA on UcCRC. Methods:HT-29 cells were treated with different concentrations(0,10,20,30, 40 mmol/ L)of 5-ASA. Cell proliferation was measured by CCK-8 assay. Cell apoptosis was determined by TUNEL method. Cell cycle was analyzed by flow cytometry. Expressions of cell mitotic regulators AuroraB and BubR1 were determined by immunohistochemistry. Results:Proliferation inhibition rates and apoptosis rates of HT-29 cells in 5-ASA 10,20,30,40 mmol/ L groups were increased with increase in concentration of 5-ASA(P ﹤ 0. 05). Proportions of cells in phase G0 / G1 in 5-ASA 30,40 mmol/ L groups were significantly lower than those in 5-ASA 0,10,20 mmol/ L groups (P ﹤ 0. 05);proportions of cells in phase S in 5-ASA 0,10,20,30 mmol/ L groups were significantly lower than that in 5-ASA 40 mmol/ L group(P ﹤ 0. 05);while proportions of cells in phase G2 / M in 5-ASA 30,40 mmol/ L groups were significantly higher than those in 5-ASA 0,10,20 mmol/ L groups(P ﹤ 0. 05). Mean optical density(MOD)values of AuroraB and BubR1 were decreased with increase in concentration of 5-ASA(P ﹤ 0. 05). Concentration of 5-ASA was positively correlated with proliferation inhibition rate and apoptosis rate of HT-29 cells(P ﹤ 0. 05),but was negatively correlated with MOD values of AuroraB and BubR1( P ﹤ 0. 05). MOD values of AuroraB and BubR1 were negatively correlated with proliferation inhibition rate and apoptosis rate of HT-29 cells as well as proportion of cells in phase G2/ M (P ﹤0. 05),but were positively correlated with proportion of cells in phase G0/ G1(P ﹤0. 05). MOD value of AuroraB was positively correlated with MOD value of BubR1(P ﹤ 0. 05). Conclusions:5-ASA can inhibit proliferation and induce apoptosis in HT-29 cells,the mechanism may be related to inhibiting expressions of AuroraB and BubR1 and the resulted effect on cell cycle.