Effects of CDX2 on cell growth, apoptosis and autophagy of SW480 and HCT-116 cells and on COX-2 expression in vitro
AIM: To investigate the effect and mechanism of CDX2 on the growth, apoptosis and autophagy of human colon cancer cell lines SW480 and HCT-116 and on the expression of COX-2 proteins in vitro. METHODS: Cell cycle analysis and apoptosis rates were evaluated by flow cytometery (FCM) and cell proliferative inhibition rates were measured by MTT assay. After treatment of CDX2 for 48 h, the morphological features of cells including apoptosis and autophagy were observed using transmission electron microscopy (TEM). The expressions of COX-2 proteins were detected by immunocytochemistry. RESULTS: Within the dose range from 5 to 40 mg/L, CDX2 inhibited the proliferation of SW480 and HCT-116 cells in a time- and dose-dependent manner. Cell cycle redistributed after the cells were treated with CDX2 at different doses (2.5, 5, 10, 20 and 40 mg/L) for 48 h and the rate of apoptosis increased. Phases of G0/G1 were prolonged and S and G2 were significantly shortened compared with those in control group (P ＜ 0.05). Light microscopy observations of anchorage-dependent cells grown on cover slips and stained with H & E and PAS showed that CDX2 induced some cells into maturation, especially HCT-116 cells which were low differentiated cells. Transmission electron microscopy revealed apoptosis and autophagy, with the two co-existing in a single cell. IHC showed that both SW480 and HCT-116 cells expressed COX-2 proteins. After the cells were treated with CDX2 for 48 h, the expression rates of COX-2 were significantly attenuated compared with that in control group (P ＜ 0.05). CONCLUSION: CDX2 inhibits cell growth, alters cell cycle and motivates cells to be well-differentiated by down-regulating the expression of COX-2 in SW480 and HCT-116 cell lines and thus inducing apoptosis and/or autophagy. Apoptosis and/or autophagy may be the main mechanism by which CDX2 serves as a tumor-suppressor.
NETL
NSTL
万方数据
维普
