PKM2 gene regulates the behavior of pancreatic cancer cells via mitogen-activated protein kinase pathways

Abstract

The aim of the current study was to investigate the effect of the PKM2 gene on the proliferation, invasion, migration and apoptosis of Panc-1 and Sw1990 pancreatic cancer cells via its interaction with the mitogen-activated protein kinases (MAPKs) signaling pathways. The expression levels of PKM2 protein in pancreatic cancer cells and the corresponding normal tissues was determined with western blot analysis. Immunohistochemical analysis of PKM2 expression was carried out in paraffin-embedded sections of pancreatic cancer tissue. Two human pancreatic cancer cell lines were cultured in vitro, and a small interfering RNA (siRNA) was designed for the PKM2 gene and transfected into the cells. Cell proliferation was measured via an MTT assay, cell migration and invasion was measured via Transwell® chambers, and the effect of PKM2 on apoptosis was detected from B-cell lymphoma 2 (Bcl-2) and Bcl-2-associated X protein expression levels. Protein expression levels of the MAPK pathway proteins extracellular signal-regulated kinase 1/2 (ERK1/2), p38 and c-Jun N-terminal kinase (JNK) and their phosphorylated forms were measured via western blot analysis. The expression level of PKM2 was significantly upregulated in the pancreatic cancer tissue compared with that of the corresponding normal tissue. Downregulation of PKM2 expression reduced the proliferation, migration and invasion of pancreatic cancer cell lines, while increasing the levels of apoptosis. Additionally, the expression levels of the phosphorylated-(p-)ERK1/2 and p-p38 of the MAPK pathway in the PKM2 siRNA groups were markedly downregulated compared with those of the controls; however, the expression levels of ERK1/2, p38, JNK, p-p38 and p-JNK had no significantly changes compared with those of the control groups. In summary, the PKM2 gene has an important role in the proliferation, invasion, migration and apoptosis of Panc-1 and Sw1990 pancreatic cancer cells, which may be associated with the expression of ERK1/2 and p38 of the MAPK signaling cascade.