Metformin Mitigated Obesity-Driven Cancer Aggressiveness in Tumor-Bearing Mice
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/...
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| Format: | Article |
| Language: | English |
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MDPI AG
2022-08-01
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| Series: | International Journal of Molecular Sciences |
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| Online Access: | https://www.mdpi.com/1422-0067/23/16/9134 |
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| author | Chun-Jung Chen Chih-Cheng Wu Cheng-Yi Chang Jian-Ri Li Yen-Chuan Ou Wen-Ying Chen Su-Lan Liao Jiaan-Der Wang |
| author_facet | Chun-Jung Chen Chih-Cheng Wu Cheng-Yi Chang Jian-Ri Li Yen-Chuan Ou Wen-Ying Chen Su-Lan Liao Jiaan-Der Wang |
| author_sort | Chun-Jung Chen |
| collection | DOAJ |
| description | 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. |
| first_indexed | 2024-03-09T09:55:22Z |
| format | Article |
| id | doaj.art-68ab1f9187274f8e8e49bd2965ac1931 |
| institution | Directory Open Access Journal |
| issn | 1661-6596 1422-0067 |
| language | English |
| last_indexed | 2024-03-09T09:55:22Z |
| publishDate | 2022-08-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | International Journal of Molecular Sciences |
| spelling | doaj.art-68ab1f9187274f8e8e49bd2965ac19312023-12-01T23:47:35ZengMDPI AGInternational Journal of Molecular Sciences1661-65961422-00672022-08-012316913410.3390/ijms23169134Metformin Mitigated Obesity-Driven Cancer Aggressiveness in Tumor-Bearing MiceChun-Jung Chen0Chih-Cheng Wu1Cheng-Yi Chang2Jian-Ri Li3Yen-Chuan Ou4Wen-Ying Chen5Su-Lan Liao6Jiaan-Der Wang7Department of Medical Research, Taichung Veterans General Hospital, Taichung City 407, TaiwanDepartment of Anesthesiology, Taichung Veterans General Hospital, Taichung City 407, TaiwanDepartment of Surgery, Feng Yuan Hospital, Taichung City 420, TaiwanDivision of Urology, Taichung Veterans General Hospital, Taichung City 407, TaiwanDivision of Urology, Tungs’ Taichung Metro Harbor Hospital, Taichung City 435, TaiwanDepartment of Veterinary Medicine, National Chung Hsing University, Taichung City 402, TaiwanDepartment of Medical Research, Taichung Veterans General Hospital, Taichung City 407, TaiwanChildren’s Medical Center, Taichung Veterans General Hospital, Taichung City 407, TaiwanMetformin 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.https://www.mdpi.com/1422-0067/23/16/9134salignancymetabolismmetforminneutrophilsneutrophil extracellular trapsobesity |
| spellingShingle | Chun-Jung Chen Chih-Cheng Wu Cheng-Yi Chang Jian-Ri Li Yen-Chuan Ou Wen-Ying Chen Su-Lan Liao Jiaan-Der Wang Metformin Mitigated Obesity-Driven Cancer Aggressiveness in Tumor-Bearing Mice International Journal of Molecular Sciences salignancy metabolism metformin neutrophils neutrophil extracellular traps obesity |
| title | Metformin Mitigated Obesity-Driven Cancer Aggressiveness in Tumor-Bearing Mice |
| title_full | Metformin Mitigated Obesity-Driven Cancer Aggressiveness in Tumor-Bearing Mice |
| title_fullStr | Metformin Mitigated Obesity-Driven Cancer Aggressiveness in Tumor-Bearing Mice |
| title_full_unstemmed | Metformin Mitigated Obesity-Driven Cancer Aggressiveness in Tumor-Bearing Mice |
| title_short | Metformin Mitigated Obesity-Driven Cancer Aggressiveness in Tumor-Bearing Mice |
| title_sort | metformin mitigated obesity driven cancer aggressiveness in tumor bearing mice |
| topic | salignancy metabolism metformin neutrophils neutrophil extracellular traps obesity |
| url | https://www.mdpi.com/1422-0067/23/16/9134 |
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