Inhibitory effect of sulindac on the proliferation of HT‐29 colon adenocarcinoma cells: Effects on cell cycle and apoptosis

Abstract

OBJECTIVE: To investigate: (i) the effect of sulindac on the proliferation of HT-29 cells; and (ii) the antineoplastic mechanisms of sulindac. METHODS: The MTT colorimetric assay was used to examine the effect of sulindac on the proliferation of HT-29 cells. Flow cytometry was used for examining the cell cycle distribution. Flow cytometry, transmission electron microscopy and DNA electrophoresis were used to determine whether sulindac induces cell apoptosis. RESULTS: Sulindac inhibited cell proliferation in a time- and dose-dependent manner. After treatment with 0.3, 0.6, 0.9 and 1.2 mmol/L sulindac for 72 h, the inhibition rates reached 16, 38, 62.3 and 92.2%, respectively. After treatment with 1.2 mmol/L sulindac for 24, 48 and 72 h, the inhibition rates reached 32.4, 71.3 and 92.2%, respectively (P < 0.05). Sulindac increased the proportion of cells in the G0/G1 phase and decreased the proportion of cells in the S phase of the cell cycle. After treatment with 1.2 mmol/L sulindac for 48 h, the proportion of cells in the G0/G1 phase increased from 32.5 to 70.5% and the S phase decreased from 43.1 to 11.3% compared with the control cells (P < 0.01). Flow cytometry, DNA electrophoresis and transmission electron microscopy all demonstrated that sulindac could induce apoptosis of the HT-29 cell line. After treatment with 0.3, 0.6 and 1.2 mmol/L sulindac for 48 h, the proportion of apoptotic cells reached 5.8, 7.6 and 11.7%, compared with 2.9% in the control group; after treatment for 72 h, the proportion of apoptotic cells increased to 12.5, 15.4% and 24.2%, respectively (P < 0.05). All effects were time and dose dependent. CONCLUSIONS: The colon adenocarcinoma HT-29 cell line can be inhibited by sulindac and the antitumor mechanism may be related to changing cell cycle distribution and inducing cell apoptosis.