Inhibition Of Cyclooxygenase-1 Expression Stimulates Mitochondrial-Induced Apoptosis Through NF-κB Signaling Pathways In Colon Cancer Cells

Colorectal cancer(CRC)is one kind of the common malignant tumor,with high disease incident and fatality rate,which has not obvious symptom at the early stage.Therefore,understanding the molecular regulation features of CRC helps researches in Disease Pathology and recognizing mechanism of new therapeutic target.It is also a potential biomarkers of earlier-discover,earlier-prevention and clinical intervention of CRC.A study of epidemiology shows that cyclooxygenase-1(COX-1)has positive effect over appearance of CRC.Yet,the exact mechanism that COX-1 gene inoloved in CRC cells is not yet clear.In this research,we found that COX-1 gene dramatically increased in tissues of CRC and CRC cell lines,HCT116 cells and HT29 cells.Thus,in order to confirm whether development of the cancer could be retarded or stopped by selectively inhibiting the expression of COX-1 gene,and clear the mechanism of COX-1 applies over CRC cells.we down-regulated the expression of COX-1employ sh RNA.The results show that specific knock-down of COX-1 in HCT116 and HT29 CRC cells affected the function of mitochondria,led to inhibition of ATP production,induced generation of ROS in cells,triggered the caspase-dependent mitochondrial apoptosis,and eventually triggered cytochrome C released from mitochondria to cytoplasm.Moreover,the Phosphorylation of sub-unit of Nuclear transcription factor-κB(NF-κB)p65 was inhibited the espression of COX-1.Meanwhile the expression of Anti-apoptotic protein Bcl-2 was inhibited and the expression of Pro-apoptotic protein was imcreased.In conclusion,our research suggested that specific COX-1 inhibition significantly reduced cell death,which is caused by cell cycle arrest and mitochondria dysfunction.This is also related to activation in cascade reaction of caspase dependence apoptosis,and the activation of signal pathway inside Mitochondria is needed to inhibit vitality of NF-κB.These results provide the potential evidence for preventing CRC.