Department of Oncology, The First Affiliated Hospital of Anhui Medical University, Hefei, Anhui 230022, P.R. China.
Int J Mol Med. 2019 Jan;43(1):475-488. doi: 10.3892/ijmm.2018.3936. Epub 2018 Oct 16.
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‑1α (HIF‑1α) at the mRNA and protein levels in addition to inhibiting proliferation (P<0.05), whereas apoptosis was notably increased. Furthermore, HIF‑1α and PKM2‑knockdown increased cell apoptosis without inhibiting COX‑2 expression. PKM2 inhibition did not have a marked effect on COX‑2 and HIF‑1α expression. In conclusion, the results of the present study suggested that HIF‑1α/PKM2 pathway‑associated metabolic changes may facilitate COX‑2‑induced apoptosis resistance in HCC cells.
丙酮酸激酶 M2 同工酶（PKM2）是有氧糖酵解的关键组成部分，据报道其可调节细胞凋亡。然而，PKM2 是否参与环氧合酶-2（COX-2）诱导的肝癌（HCC）细胞凋亡抵抗尚不清楚。在本研究中，与相邻肝组织相比，肝癌组织中 COX-2 和 PKM2 的表达明显升高（P<0.05）。此外，其表达与更差的临床病理特征呈正相关，这表明 HCC 患者预后不良。COX-2 敲低显著降低了 PKM2 和缺氧诱导因子-1α（HIF-1α）的 mRNA 和蛋白水平的表达，同时抑制了增殖（P<0.05），而凋亡明显增加。此外，HIF-1α和 PKM2 敲低在不抑制 COX-2 表达的情况下增加了细胞凋亡。PKM2 抑制对 COX-2 和 HIF-1α 的表达没有显著影响。综上所述，本研究结果表明，HIF-1α/PKM2 通路相关的代谢变化可能有助于 COX-2 诱导的 HCC 细胞凋亡抵抗。
