Pancreatic cancer is a highly aggressive tumor characterized by enhanced aerobic glycolysis. AMP-activated protein kinase (AMPK), which is identified as a well-known regulator of glycolysis, plays an essential role in tumorigenesis. In the present study, we aim to explore the function of AMPK in pancreatic cancer cells and attempt to clarify the possible underlying mechanism. The Cancer Genome Atlas (TCGA) data showed that elevated AMPK expression highly correlated with lower median survival time. In an in vitro study, inhibition of AMPK blocked the proliferation, migration, and invasion ability of four cell lines under normoxia and hypoxia. Additionally, AMPK suppression led to cell cycle arrest and remarkably induced apoptosis. Furthermore, the lactic acid content, ATP content, and the glucose consumption rate were significantly reduced in all four cell lines under different conditions, accompanied by down-regulation of glycolytic biomarkers including phosphorylated mammalian target of rapamycin (p-mTOR)/total mTOR (t-mTOR), Pyruvate kinase M2 (Pkm2), and Hexokinase 2 (Hk2). Collectively, our data showed that AMPK activation is highly involved in pancreatic cancer progression and exerts its pro-tumorigenic functions partly by sustaining glycolytic activity. Hence, AMPK is expected to be a potential therapeutic target for pancreatic cancer.
Keywords: AMPK; aerobic glycolysis; hypoxia; mTOR; pancreatic cancer.