2. Academic Validation
  3. Metformin sensitizes AML cells to chemotherapy through blocking mitochondrial transfer from stromal cells to AML cells

Metformin sensitizes AML cells to chemotherapy through blocking mitochondrial transfer from stromal cells to AML cells

  • Cancer Lett. 2022 Apr 28;532:215582. doi: 10.1016/j.canlet.2022.215582.
Ruolan You 1,  Bin Wang 2,  Ping Chen 3,  Xiaoming Zheng 1,  Diyu Hou 1,  Xiaoting Wang 1,  Beiying Zhang 1,  Ling Chen 1,  Dongliang Li 4,  Xinjian Lin 5,  Huifang Huang 6
Affiliations

Affiliations

  • 1 Central Laboratory, Fujian Medical University Union Hospital, Fuzhou, Fujian, 350001, China.
  • 2 Central Laboratory, Fujian Medical University Union Hospital, Fuzhou, Fujian, 350001, China; Clinical Laboratory, Fujian Children's Hospital, Fuzhou, Fujian, 350011, China.
  • 3 Fujian Institute of Hematology, Fujian Provincial Key Laboratory of Hematology, Fujian Medical University Union Hospital, Fuzhou, Fujian, 350001, China.
  • 4 Department of Hepatobiliary Disease, The 900th Hospital of the People's Liberation Army Joint Service Support Force, Fuzhou, Fujian, 350025, China.
  • 5 Key Laboratory of Gastrointestinal Cancer (Fujian Medical University), Ministry of Education, Fuzhou, Fujian, 350122, China. Electronic address: xlin@fjmu.edu.cn.
  • 6 Central Laboratory, Fujian Medical University Union Hospital, Fuzhou, Fujian, 350001, China. Electronic address: huanghuif@fjmu.edu.cn.
PMID: 35122876 DOI: 10.1016/j.canlet.2022.215582
Abstract

Interaction between stromal cells and acute myeloid leukemia (AML) cells in bone marrow (BM) is known to contribute importantly to chemoresistance and disease recurrence. Therefore, disruption of a crosstalk between AML cells and BM microenvironment may offer a promising therapeutic strategy for AML treatment. Here, we demonstrate that in a niche-like co-culture system, AML cells took up functional mitochondria from bone marrow stromal cells (BMSCs) and inhibition of such mitochondrial transfer by metformin, the most commonly prescribed drug for type 2 diabetes mellitus, significantly enhanced the chemosensitivity of AML cells co-cultured with BMSCs. The chemo-sensitizing effect of metformin was acted through reducing the mitochondrial transfer and mitochondrial Oxidative Phosphorylation (OXPHOS) in the recipient AML cells. In addition, metformin potentiated the antitumor efficacy of cytarabine (Ara-C) in vivo in an NCG immunodeficient mouse xenograft model by inhibiting the mitochondrial transfer and OXPHOS activity in the engrafted human AML cells. Altogether, this study identifies a potential application of metformin in sensitizing AML cells to chemotherapy and unveils a novel mechanism by which metformin executes such effect via blocking the mitochondrial transfer from stromal cells to AML cells.

Keywords

Chemo-sensitizing effect; Chemotherapy resistance; Metformin; Mitochondrial transfer.

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