2. Academic Validation
  3. Metformin Mitigated Obesity-Driven Cancer Aggressiveness in Tumor-Bearing Mice

Metformin Mitigated Obesity-Driven Cancer Aggressiveness in Tumor-Bearing Mice

  • Int J Mol Sci. 2022 Aug 15;23(16):9134. doi: 10.3390/ijms23169134.
Chun-Jung Chen 1 2,  Chih-Cheng Wu 3 4 5,  Cheng-Yi Chang 6 7,  Jian-Ri Li 8,  Yen-Chuan Ou 9,  Wen-Ying Chen 7,  Su-Lan Liao 1,  Jiaan-Der Wang 10 11
Affiliations

Affiliations

  • 1 Department of Medical Research, Taichung Veterans General Hospital, Taichung City 407, Taiwan.
  • 2 Department of Medical Laboratory Science and Biotechnology, China Medical University, Taichung City 404, Taiwan.
  • 3 Department of Anesthesiology, Taichung Veterans General Hospital, Taichung City 407, Taiwan.
  • 4 Department of Financial Engineering, Providence University, Taichung City 433, Taiwan.
  • 5 Department of Data Science and Big Data Analytics, Providence University, Taichung City 433, Taiwan.
  • 6 Department of Surgery, Feng Yuan Hospital, Taichung City 420, Taiwan.
  • 7 Department of Veterinary Medicine, National Chung Hsing University, Taichung City 402, Taiwan.
  • 8 Division of Urology, Taichung Veterans General Hospital, Taichung City 407, Taiwan.
  • 9 Division of Urology, Tungs' Taichung Metro Harbor Hospital, Taichung City 435, Taiwan.
  • 10 Children's Medical Center, Taichung Veterans General Hospital, Taichung City 407, Taiwan.
  • 11 Department of Industrial Engineering and Enterprise Information, Tunghai University, Taichung City 407, Taiwan.
PMID: 36012397 DOI: 10.3390/ijms23169134
Abstract

Metformin may offer benefits to certain Cancer populations experiencing metabolic abnormalities. To extend the Anticancer studies of metformin, a tumor model was established through the implantation of murine Lewis Lung Carcinoma (LLC) cells to Normal Diet (ND)-fed and High-Fat Diet (HFD)-fed C57BL/6 mice. The HFD-fed mice displayed metabolic and pro-inflammatory alterations together with accompanying aggressive tumor growth. Metformin mitigated tumor growth in HFD-fed mice, paralleled by reductions in circulating glucose, Insulin, soluble P-selectin, TGF-β1 and High Mobility Group Box-1 (HMGB1), as well as tumor expression of cell proliferation, aerobic glycolysis, glutaminolysis, platelets and neutrophils molecules. The suppressive effects of metformin on cell proliferation, migration and oncogenic signaling molecules were confirmed in cell study. Moreover, tumor-bearing HFD-fed mice had higher contents of circulating and tumor immunopositivity of Neutrophil Extracellular Traps (NETs)-associated molecules, with a suppressive effect from metformin. Data taken from neutrophil studies confirmed the inhibitory effect that metformin has on NET formation induced by HMGB1. Furthermore, HMGB1 was identified as a promoting molecule to boost the transition process towards NETs. The current study shows that metabolic, pro-inflammatory and NET alterations appear to play roles in the obesity-driven aggressiveness of Cancer, while also representing candidate targets for Anticancer potential of metformin.

Keywords

metabolism; metformin; neutrophil extracellular traps; neutrophils; obesity; salignancy.

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