Functional characteristics of autophagy in pancreatic cancer induced by glutamate metabolism in pancreatic stellate cells

J Int Med Res. 2020 Apr;48(4):300060519865368. doi: 10.1177/0300060519865368. Epub 2019 Dec 19.

Abstract

Objective: To observe the effects of glutaminase (GLS) inhibitors on autophagy and proliferation of pancreatic stellate cells, and to explore their functions in pancreatic cancer.

Methods: Pancreatic cancer cells were divided into two groups. Group A was the control untreated group, and group B cells were treated with GLS inhibitors. Western blotting was used to detect the expression of Atg5, Bcl-2, Bax, and Bid proteins. The bromodeoxyuridine assay and scratch test were employed to investigate cell proliferation and invasion, respectively. The expression of E-cadherin, vimentin, cell adhesion molecule 2 (CADM2), and Snail protein was investigated by immunofluorescence.

Results: The expression of Atg5, Bax, and Bid was higher in group A than in group B, while Bcl-2 expression was lower in group A than in group B. Group A cells demonstrated greater proliferation and invasion than group B cells. The expression of E-cadherin was lower in group A cells than group B cells, while vimentin, CADM2, and Snail were expressed at higher levels in group A than group B cells.

Conclusion: The inhibition of glutamine isozymes reduces autophagy and apoptosis in astrocytes, and inhibits pancreatic cancer cell proliferation and metastasis, while reducing their invasiveness.

Keywords: Autophagy; cell adhesion molecule 2; glutamate metabolism; glutaminase; pancreatic cancer; pancreatic stellate cells.

MeSH terms

  • Apoptosis
  • Autophagy
  • Cell Line, Tumor
  • Cell Movement
  • Cell Proliferation
  • Glutamates
  • Humans
  • Pancreatic Neoplasms* / genetics
  • Pancreatic Stellate Cells*

Substances

  • Glutamates