RESUMEN
The prognosis of patients with colorectal cancer (CRC) remains poor owing to diagnosis typically occurring at advanced stages of the disease. The understanding of the molecular regulatory signatures of CRC may lead to the identification of biomarkers for the early detection, prevention and clinical intervention of CRC. Epidemiological studies have indicated that cyclooxygenase1 (COX1) serves an active function in colon carcinogenesis. However, the molecular mechanism underlying COX1 regulation in CRC remains unknown. In the present study, COX1 was identified to be markedly upregulated in colorectal tissues of patients with CRC, and in the CRC cell lines HCT116 and HT29. To determine the function of COX1 in cancer development, short hairpin RNA knockdown of COX1 was employed in HCT116 and HT29 CRC cells in the present study. The results demonstrated that silencing of COX1 depolarized the mitochondrial membrane potential, inhibited adenosine triphosphate production, induced the generation of intracellular reactive oxygen species and triggered caspasedependent mitochondrial apoptosis. Furthermore, depletion of COX1 suppressed antiapoptotic Bcell lymphoma 2 and enhanced proapoptotic Bcl2associated X protein expression by inhibiting the p65 subunit phosphorylation of nuclear factor κB (NFκB). Taken together, the results of the present study indicated that COX1 inhibition significantly triggered cell death by destroying the mitochondrial function that is associated with deactivation of the NFκB signaling pathway. These results suggest COX1 as a potential anticancer target in CRC.