Juzaowan Suppresses Glycolysis in Breast Cancer Cells by Inhibiting the STAT3/C-Myc Axis.

Abstract

Background: Breast cancer (BC) is characterized by an increasing incidence and mortality rate. Juzaowan inhibits various malignant processes, although its mechanism in BC remains unclear.

Methods: To evaluate the impact of Juzaowan on biological functions of BC cells, cellular assays were done to assess proliferation, migration, invasion, and apoptosis. Bioinformatics was used to identify signaling pathways affected by active ingredients of Juzaowan. BC cells were treated with Juzaowan. Western blot assayed lactate production, glucose consumption, and expression of proteins related to glycolytic pathway and STAT3/C-Myc axis.

Results: Juzaowan suppressed BC cell proliferation and increased apoptosis. It downregulated anti-apoptotic protein BCL2 while upregulating pro-apoptotic proteins Bax and cleaved caspase 3. Juzaowan significantly inhibited BC cell migration and invasion. Significant upregulation of E-cadherin and significant downregulation of E-cadherin-binding protein ZEB1, N-cadherin, and vimentin were observed. Bioinformatics analysis and cellular experiments confirmed inhibition of Juzaowan on BC cell glucose uptake and glycolytic pathways-related key metabolic enzymes (GLUT1, PKM2, LDH) expressions. Western blot revealed that Juzaowan induced metabolic alterations in BC cells by impeding STAT3/C-Myc axis.

Conclusion: This study elucidated molecular mechanisms of Juzaowan inhibiting BC cell glycolysis by repressing STAT3/C-Myc axis, thus suppressing malignant progression. These findings supported clinical applications of Juzaowan.