Differences in glucose concentration shows new perspectives in gastric cancer metabolism

Toxicol In Vitro. 2022 Aug:82:105357. doi: 10.1016/j.tiv.2022.105357. Epub 2022 Apr 12.

Abstract

Gastric cancer (GC) is among the deadliest cancers worldwide despite available therapies, highlighting the need for novel therapies and pharmacological agents. Metabolic deregulation is a potential study area for new anticancer targets, but the in vitro metabolic studies are controversial, as different ranges of glucose used in the culture media can influence results. In this study, we evaluated cellular viability, glucose uptake, and LDH activity in gastric cancer cell lines when exposed to different glucose concentrations: high (HG, 25mM), low (LG, 5.5mM), and free (FG, 0mM) glucose media. Moreover, we evaluated how glucose variations may influence cellular phenotype and the expression of genes related to epithelial-mesenchymal transition (EMT), metabolism, and cancer development in metastatic GC cells (AGP-01). Results showed that metastatic cells exposed to FG medium evidenced higher alterations when compared to other cell lines. Most phenotypic assays did not show difference when exposed to either HG or LG media. However, gene expression profile of cells exposed to LG revealed differences in mRNA levels of metabolism-related genes when compared to HG medium. According to our results, we recommend using LG medium for metabolic studies since the glucose concentration is closer to physiological levels. These findings point out new relevant targets in metabolic reprogramming that can be alternatives to current chemotherapies in patients with metastatic GC.

Keywords: Aerobic pathways; Cancer microenvironment; Gastric cancer; Glucose deprivation; Metabolism reprogramming.

MeSH terms

  • Cell Line, Tumor
  • Cell Survival
  • Epithelial-Mesenchymal Transition
  • Glucose / pharmacology
  • Humans
  • Stomach Neoplasms* / metabolism

Substances

  • Glucose