COX-2 induces apoptosis-resistance in hepatocellular carcinoma cells via the HIF-1/PKM2 pathway

The pyruvate kinase M2 isoform (PKM2) is a key component of aerobic glycolysis and has been reported to regulate apoptosis. However, it is unclear whether PKM2 is involved in cyclooxygenase-2 (COX-2) induced apoptosis-resistance in hepatocellular carcinoma (HCC) cells. In the present study, it was observed that COX-2 and PKM2 were significantly elevated in hepatocellular carcinoma tissues compared with adjacent liver tissues (P<0.05). Furthermore, their expression was positively associated with worse clinicopathological characteristics, which indicates poor prognosis in patients with HCC. COX-2 knockdown significantly reduced the expression of PKM2 and hypoxia inducible factor-1 (HIF-1) at the mRNA and protein levels in addition to inhibiting proliferation (P<0.05), whereas apoptosis was notably increased. Furthermore, HIF-1 and PKM2-knockdown increased cell apoptosis without inhibiting COX-2 expression. PKM2 inhibition did not have a marked effect on COX-2 and HIF-1 expression. In conclusion, the results of the present study suggested that HIF-1/PKM2 pathway-associated metabolic changes may facilitate COX-2-induced apoptosis resistance in HCC cells.