The Effects Of Sulindac On Proliferation,Apoptosis And β-catenin Protein Expression Of Colon Cancer Cells HT-29

Objective:To observe the effects of sulindac on proliferation, apoptosis andβ-catenin protein expression in the human colorectal carcinoma cell line HT-29 and to explore the possible anti-cancer mechanism of sulindac and provide further evidence for its clinical application.Methods:1. MTT colorimetric assay was used to examine the effect of sulindac on the proliferation of the colorectal carcinoma cell line HT-29.2. The effect of sulindac induced-apoptosis on the colorectal carcinoma cell line HT-29 was detected by flow cytometry.3. Transmission electron microscopy was used to observe the morphology changes of HT-29 cells treated with sulindac.4. Western blotting was used to examineβ-catenin protein level in HT-29 cells before and after sulindac treatment.Results:1. Sulindac significantly inhibited the proliferation of HT-29 cells in a time-and dose-dependent manner after incubation for 24,48,72 hours compared with the control group (P<0.05).2. Apoptosis rate in the blank control group was 1.1%±0.5%, and apoptosis rate of DMSO control group after incubation for 8,24,48 hours was 2.1%±0.6%, 2.2%±0.3%,2.9%±0.6%, respectively, which had no statistically significant difference between the two control groups (P>0.05). Apoptosis rate of sulindac group after incubation for 8,24,48 hours was 12.2%±0.6%,14.9%±0.5%, 24.5%±0.5%, respectively, markedly higher than that of the two control groups (P<0.01).3. Chromatin condensation, karyopyknosis, nuclear fragmentation and apoptotic bodies were observed in sulindac treated HT-29 cells, while the blank control groups had no apparent changes.4. Western blotting showed that the protein level ofβ-catenin in HT-29 cells was reduced after sulindac treated compared with the control group (P<0.05), and the inhibition was time-dependent.Conclusion:Sulindac could significantly inhibit the proliferation of HT-29 cells, and the mechanism of inhibition may be related to induction of apoptosis. Moreover, downregulation ofβ-catenin protein expression was one of the mechanisms of sulindac induced apoptosis in tumor cells.