Inhibitory effect of glucocorticoid receptor on colorectal cancer growth by inhibiting glycolysis through autophagy

Abstract

Glucocorticoid receptor (GR) affects the development and progression of most malignant tumors by regulating autophagy. The GR gene is not expressed in colon cancer. To explore the role and mechanism of GR in colon cancer, dexamethasone (DXM) was used to stimulate the expression of GR. The expression of the autophagy markers Beclin 1 (BECN1) and light chain 3 (LC3B) was then detected by qRT-PCR and western blotting. The effects of the differential expression of GR on autophagy, ATP, lactic acid accumulation, and glucose utilization in colon cancer cells were studied. Differential expression of GR affected glycolysis, apoptosis, and migration of colon cancer cells, as determined by flow cytometry and cell viability and migration assays, respectively. The DXM-induced elevation of GR expression significantly promoted the expression of the autophagy-related genes BECN1 and LC3B, and decreased the ATP production, lactic acid accumulation, and glucose uptake in colon cancer cells. These events resulted in the inhibition of colon cancer cell growth, which also involved decreased cell viability and mobility and increased rate of apoptosis. These findings indicate that the GR can promote autophagy and inhibit glycolysis in colon cancer cells, reduce their proliferation and migration, and promote their apoptosis in vitro.