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Metformin, an antidiabetic agent reduces growth of cutaneous squamous cell carcinoma by targeting mTOR signaling

Sandeep C Chaudhary1, Deepali Kurundkar, Craig A Elmets

  • 1Department of Dermatology, University of Alabama at Birmingham, Birmingham, AL, USA.

Photochemistry and Photobiology
|May 1, 2012
PubMed

Insights

Metformin, a diabetes drug, effectively inhibits squamous cell carcinoma (SCC) growth by reducing cell proliferation and increasing cell death. It works by suppressing key signaling pathways like NFkB and mTOR.

Area of Science:

  • Oncology
  • Pharmacology
  • Molecular Biology

Background:

  • Metformin is a common Type-II diabetes medication.
  • Metformin exhibits antiproliferative and pro-apoptotic properties in tumor cells, suggesting potential in cancer chemoprevention.

Purpose of the Study:

  • To investigate the efficacy of metformin in inhibiting human epidermoid A431 tumor xenograft growth.
  • To elucidate the molecular mechanisms underlying metformin's antitumor effects.

Main Methods:

  • Administration of metformin to nu/nu mice bearing human epidermoid A431 tumor xenografts.
  • Assessment of tumor growth, proliferative biomarkers (PCNA, cyclins D1/B1), apoptotic markers (Bax:Bcl2 ratio), and key signaling pathways (NFkB, mTOR, MAP kinase, AKT).

Main Results:

  • Metformin significantly inhibited tumor xenograft growth.
  • Reduced levels of PCNA and cyclins D1/B1 were observed, indicating decreased proliferation.
  • Enhanced apoptotic cell death and an increased Bax:Bcl2 ratio were noted.
  • Metformin suppressed NFkB and mTOR signaling pathways, evidenced by decreased phosphorylation of IKBα, p70S6K, 4E-BP-1, and GSK3β.
  • Inhibition of MAP kinase (ERK/p38) and AKT signaling pathways was also observed.

Conclusions:

  • Metformin demonstrates significant antitumor activity against human epidermoid xenografts.
  • The mechanism involves the suppression of NFkB and mTOR signaling pathways.
  • Metformin holds potential as a chemopreventive agent for squamous cell carcinoma (SCC).

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