Downregulation of Glutaminase 1 (Gls1) Inhibits Proliferation, Clonogenicity, and Migration of Aggressive Mda-Mb Breast Cancer Cells by Increasing P21 and Decreasing Integrin-Β1 Expression

Abstract

Objective: Glutamine metabolism is an important pathway in cell proliferation and tumor progression. The first enzyme to be converted in the process of glutamine metabolism, glutaminase 1 (GLS1), exhibits increased expression in many types of cancer, including breast cancer. Triple-negative breast cancer (TNBC) is an aggressive breast cancer subtype with high glutamine metabolic activity. The aim of this research was to examine the effects on glutamine metabolism and carcinogenic properties following small interfering RNA (siRNA)-mediated inhibition of GLS1 in glutamine-dependent TNBC.Materials and Methods: The effects on cell proliferation, migration, apoptosis, colony formation, and the cell cycle of MDA-MB-231 cells using different siRNAs targeting GLS1 were analyzed using an MTS assay, a wound-healing assay, clo-nogenic analysis, and annexin V and propidium iodide staining methods. The protein expression of GLS1, integrin beta 1 (beta 1), caspase-3, and p21 were examined using western blot analysis and flow cytometry.Results: The findings revealed that cell viability, migration, and colony formation were significantly suppressed in MDA-MB-231 cells transfected with 2 different GLS1 siRNAs. Furthermore, the results of flow cytometry and western blot analysis demonstrated that knockdown of GLS1 induced arrest in the G0/G1 phase of the cell cycle through the p21 signaling pathway, but did not induce apoptosis.Conclusion: GLS1 is needed for cell proliferation and promotes tumor progression and growth of MDA-MB 231 cells. siRNAs may provide a means to downregulate GLS1 and offer a promising target for breast cancer therapy.