Rosiglitazone and retinoic acid inhibit proliferation and induce apoptosis in the HCT-15 human colorectal cancer cell line.

The aim of this study was to explore the effects of rosiglitazone (RSG) in combination with all-trans retinoic acid (ATRA) on the proliferation and apoptosis of the HCT-15 human colorectal cancer cell line. HCT-15 cells were divided into a blank control group, a vehicle control group and experimental groups (RSG only or ATRA only or RSG plus ATRA). Growth inhibition was examined using the MTT assay. Apoptosis and cell cycle progression were examined by flow cytometry. The expression of COX-2, MMP-7 and TIMP-1 was examined by immunocytochemistry. RSG alone inhibited HCT-15 cell proliferation in a concentration- and time-dependent manner (P<0.05). The combination of RSG and ATRA exhibited significant synergy (q>1.15). RSG or ATRA alone effectively increased the proportion of cells in the G0/G1 phase and decreased the proportion of cells in the S phase, thus inducing apoptosis (P<0.05). The combination of RSG and ATRA resulted in even stronger G1 cell cycle arrest (P<0.05). HCT-15 cells expressed COX-2, MMP-7 and TIMP-1, with positive expression rates in the control group of 66.79, 73.21 and 64.08%, respectively. After the combined application of RSG and ATRA, the positive rates significantly declined to only 19.33, 20.58 and 13.13%, respectively (P<0.01). In conclusion, the combination of RSG and ATRA reduced the expression of COX-2, MMP-7 and TIMP-1, caused cell cycle arrest at the G1 phase and induced apoptosis, which resulted in the inhibition of cell proliferation in the HCT-15 human colorectal cancer cell line.