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.