1. Academic Validation
  2. Metformin inhibits IL-6 signaling by decreasing IL-6R expression on multiple myeloma cells

Metformin inhibits IL-6 signaling by decreasing IL-6R expression on multiple myeloma cells

  • Leukemia. 2019 Nov;33(11):2695-2709. doi: 10.1038/s41375-019-0470-4.
Ameet K Mishra 1 David Dingli 2 3
Affiliations

Affiliations

  • 1 Division of Hematology, Mayo Clinic, Rochester, MN, 55905, USA.
  • 2 Division of Hematology, Mayo Clinic, Rochester, MN, 55905, USA. dingli.david@mayo.edu.
  • 3 Department of Molecular Medicine, Mayo Clinic, Rochester, MN, 55905, USA. dingli.david@mayo.edu.
Abstract

IL-6 signaling plays a crucial role in the pathogenesis of a number of diseases, including multiple myeloma, primary amyloidosis, cytokine release syndrome and other inflammatory conditions. It is central for the growth and survival of malignant plasma cells. IL-6R and IL-6ST receptors transduce IL-6 signaling. Molecular mechanisms regulating expression of IL-6R are not well understood and current therapies are based on monoclonal antibody to target IL-6 signaling. Small molecule inhibitors targeting IL-6 signaling are highly desirable. Metformin specifically decreased IL-6R expression which is mediated via AMPK, mTOR, and miR34a. This is a novel finding and adds to existing therapies targeting IL-6 signaling.

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