Abstract:

BACKGROUND: Early studies have confirmed that As2O3 can promote FOXO3a factor expression in breast cancer cells and inhibit vascular endothelial growth factor expression in tumor cells. However, the effect of As2O3 on proliferation, FOXO3a and growth factors in vascular endothelial cells remains unclear.
OBJECTIVE: To investigate the effect of silencing of FOXO3a using small RNA on inhibiting the As2O3-inhibited proliferation of human umbilical vein endothelial cells and angiogenesis.
METHODS: There were four groups in this experiment: As2O3 group, control small interfering RNA group, FOXO3a small interfering RNA group and control group. (1)In As2O3 group, human umbilical vein endothelial cells were cultured in RPMI-1640 medium containing 4 μmol/L As2O3 after adherent. (2)In control small interfering RNA group, human umbilical vein endothelial cells were cultured in RPMI-1640 medium containing 4 μmol/L As2O3 after irrelevant sequence small interfering RNA was tranfected. (3)In FOXO3a small interfering RNA group, human umbilical vein endothelial cells were cultured in RPMI-1640 medium containing 4 μmol/L As2O3 after FOXO3a specific small interfering RNA was transfected into the cells. (4)In control group, a volume of PBS equal to the original volume of As2O3 served as a control, and human umbilical vein endothelial cells were cultured in the complete medium. After that, cell proliferation was detected by CCK-8 kit; the expressions of FOXO3a protein and vascular endothelial cell growth factor proteins in human umbilical vein endothelial cells were observed by immunocytochemical method.
RESULTS AND CONCLUSION: Compared with the control group, the inhibitory effect of As2O3 on the proliferation of human umbilical vein endothelial cells was weakened by silencing of FOXO3a. Besides, As2O3 could promote FOXO3a protein expression and inhibit vascular endothelial cell expression. However, FOXO3a protein expression was inhibited obviously and protein expression of vascular endothelial growth factor was increased after FOXO3a using small interfering RNA. These results suggest that the transcription factor of FOXO3a can be an important strategy for the
inhibition of tumor cell proliferation and angiogenesis.