Frontiers in Medical Science Research, 2024, 6(6); doi: 10.25236/FMSR.2024.060604.
Liucen Li1, Yao Shen2
1College of Laboratory Medicine and Life Sciences, Wenzhou Medical University, Wenzhou, Zhejiang, China
2Key Laboratory of Laboratory Medicine, Ministry of Education, College of Laboratory Medicine and Life Sciences, Wenzhou Medical University, Wenzhou, Zhejiang, 325035, China
Metformin is a classic treatment for diabetes. In recent years, metformin has been shown to inhibit the growth of tumour cells in vitro and in vivo and to increase the sensitivity of radiotherapy and chemotherapy. This study investigated the effects of metformin on active clonogenic energy and mitochondrial function in human glioma cells U87 and U251 to provide effective data for further understanding the mechanism of metformin in the treatment of glioma. To investigate the effect of metformin on mitochondrial function in U87 and U251 glioma cells. The changes in mitochondrial membrane potential, reactive oxygen species (ROS) and oxygen consumption and respiration in U87 and U251 human glioma cells treated with metformin were determined.
Metformin; U251 cells; U87 cells; mitochondria; cell proliferation
Liucen Li, Yao Shen. Effect of metformin on mitochondrial function of glioma cells. Frontiers in Medical Science Research (2024), Vol. 6, Issue 6: 24-30. https://doi.org/10.25236/FMSR.2024.060604.
[1] Davis M E. Epidemiology and Overview of Gliomas[J]. Semin Oncol Nurs, 2018, 34(5): 420-429.
[2] Ostrom Q T, Price M, Neff C, et al. CBTRUS Statistical Report: Primary Brain and Other Central Nervous System Tumors Diagnosed in the United States in 2015-2019[J]. Neuro Oncol, 2022, 24(Suppl 5): v1-v95.
[3] Ghiaseddin A P, Shin D, Melnick K, et al. Tumor Treating Fields in the Management of Patients with Malignant Gliomas[J]. Curr Treat Options Oncol, 2020, 21(9): 76.
[4] Velásquez C, Mansouri S, Mora C, et al. Molecular and Clinical Insights into the Invasive Capacity of Glioblastoma Cells[J]. J Oncol, 2019, 2019: 1740763.
[5] Rosen J, Blau T, Grau S J, et al. Extracranial Metastases of a Cerebral Glioblastoma: A Case Report and Review of the Literature[J]. Case Rep Oncol, 2018, 11(2): 591-600.
[6] Budny A, Grochowski C, Kozłowski P, et al. Obesity as a tumour development triggering factor[J]. Ann Agric Environ Med, 2019, 26(1): 13-23.
[7] Yousef M, Tsiani E. Metformin in Lung Cancer: Review of in Vitro and in Vivo Animal Studies[J]. Cancers (Basel), 2017, 9(5).
[8] Farmer R E, Ford D, Forbes H J, et al. Metformin and cancer in type 2 diabetes: a systematic review and comprehensive bias evaluation[J]. Int J Epidemiol, 2017, 46(2): 745.
[9] Li C, Xue Y, Xi Y R, et al. Progress in the application and mechanism of metformin in treating non-small cell lung cancer[J]. Oncol Lett, 2017, 13(5): 2873-2880.
[10] Seliger C, Luber C, Gerken M, et al. Use of metformin and survival of patients with high-grade glioma [J]. Int J Cancer, 2019, 144(2): 273-280.
[11] Diers A R, Broniowska K A, Chang C F, et al. Pyruvate fuels mitochondrial respiration and proliferation of breast cancer cells: effect of monocarboxylate transporter inhibition[J]. Biochem J, 2012, 444(3): 561-71.
[12] Green A S, Chapuis N, Maciel T T, et al. The LKB1/AMPK signaling pathway has tumor suppressor activity in acute myeloid leukemia through the repression of mTOR-dependent oncogenic mRNA translation [J]. Blood, 2010, 116(20): 4262-73.
[13] Sesen J, Dahan P, Scotland S J, et al. Metformin inhibits growth of human glioblastoma cells and enhances therapeutic response[J]. PLoS One, 2015, 10(4): e0123721.
[14] Grimaldi C, Chiarini F, Tabellini G, et al. AMP-dependent kinase/mammalian target of rapamycin complex 1 signaling in T-cell acute lymphoblastic leukemia: therapeutic implications[J]. Leukemia, 2012, 26(1): 91-100.
[15] Evans J M, Donnelly L A, Emslie-Smith A M, et al. Metformin and reduced risk of cancer in diabetic patients[J]. Bmj, 2005, 330(7503): 1304-5.
[16] Isakovic A, Harhaji L, Stevanovic D, et al. Dual antiglioma action of metformin: cell cycle arrest and mitochondria-dependent apoptosis[J]. Cell Mol Life Sci, 2007, 64(10): 1290-302.
[17] Cejuela M, Martin-Castillo B, Menendez J A, et al. Metformin and Breast Cancer: Where Are We Now?[J]. Int J Mol Sci, 2022, 23(5).
[18] Spiering M J. The mystery of metformin[J]. J Biol Chem, 2019, 294(17): 6689-6691.
[19] En-Lin S, Sheng-Guo C, Hua-Qiao W. The expression of EFEMP1 in cervical carcinoma and its relationship with prognosis[J]. Gynecol Oncol, 2010, 117(3): 417-22.
[20] Salani B, Maffioli S, Hamoudane M, et al. Caveolin-1 is essential for metformin inhibitory effect on IGF1 action in non-small-cell lung cancer cells[J]. Faseb j, 2012, 26(2): 788-98.
[21] Liu X, Chhipa R R, Pooya S, et al. Discrete mechanisms of mTOR and cell cycle regulation by AMPK agonists independent of AMPK[J]. Proc Natl Acad Sci U S A, 2014, 111(4): E435-44.
[22] Sato A, Sunayama J, Okada M, et al. Glioma-initiating cell elimination by metformin activation of FOXO3 via AMPK[J]. Stem Cells Transl Med, 2012, 1(11): 811-24.
[23] Sunayama J, Sato A, Matsuda K, et al. FoxO3a functions as a key integrator of cellular signals that control glioblastoma stem-like cell differentiation and tumorigenicity[J]. Stem Cells, 2011, 29(9): 1327-37.
[24] Fuentes-Fayos A C, Me G G, Pérez-Gómez J M, et al. Metformin and simvastatin exert additive antitumour effects in glioblastoma via senescence-state: clinical and translational evidence [J]. EBioMedicine, 2023, 90: 104484.
[25] Gerthofer V, Kreutz M, Renner K, et al. Combined Modulation of Tumor Metabolism by Metformin and Diclofenac in Glioma [J]. Int J Mol Sci, 2018, 19(9).
[26] Miller B F, Thyfault J P. Exercise-Pharmacology Interactions: Metformin, Statins, and Healthspan[J]. Physiology (Bethesda), 2020, 35(5): 338-347.
[27] Jafarzadeh E, Montazeri V, Aliebrahimi S, et al. Combined regimens of cisplatin and metformin in cancer therapy: A systematic review and meta-analysis[J]. Life Sci, 2022, 304: 120680.
[28] Aldea M D, Petrushev B, Soritau O, et al. Metformin plus sorafenib highly impacts temozolomide resistant glioblastoma stem-like cells [J]. J buon, 2014, 19(2): 502-11.
[29] Harada K, Ferdous T, Harada T, et al. Metformin in combination with 5-fluorouracil suppresses tumor growth by inhibiting the Warburg effect in human oral squamous cell carcinoma [J]. Int J Oncol, 2016, 49(1): 276-84.
[30] Peng M, Huang Y, Tao T, et al. Metformin and gefitinib cooperate to inhibit bladder cancer growth via both AMPK and EGFR pathways joining at Akt and Erk[J]. Sci Rep, 2016, 6: 28611.
[31] Zhu H Q, Ma J B, Song X, et al. Metformin potentiates the anticancer activities of gemcitabine and cisplatin against cholangiocarcinoma cells in vitro and in vivo[J]. Oncol Rep, 2016, 36(6): 3488-3496.
[32] Rinaldi M, Caffo M, Minutoli L, et al. ROS and Brain Gliomas: An Overview of Potential and Innovative Therapeutic Strategies [J]. Int J Mol Sci, 2016, 17(6).
[33] De Vleeschouwer S, Bergers G. Glioblastoma: To Target the Tumor Cell or the Microenvironment? In: De Vleeschouwer S, editor. Glioblastoma [Internet]. Brisbane (AU): Codon Publications; 2017 Sep 27. Chapter 16.
[34] Arfin S, Jha N K, Jha S K, et al. Oxidative Stress in Cancer Cell Metabolism[J]. Antioxidants (Basel), 2021, 10(5).
[35] Feng S W, Chang P C, Chen H Y, et al. Exploring the Mechanism of Adjuvant Treatment of Glioblastoma Using Temozolomide and Metformin[J]. Int J Mol Sci, 2022, 23(15).