Open Access

Lack of chemopreventive efficacy of metformin in rodent models of urinary bladder, head and neck, and colon/intestine cancer

  • Authors:
    • Matthew D. Thompson
    • Ronald A. Lubet
    • David L. Mccormick
    • Margie L. Clapper
    • Ann M. Bode
    • M. Margaret Juliana
    • Fariba Moeinpour
    • Clinton J. Grubbs
  • View Affiliations

  • Published online on: July 20, 2017     https://doi.org/10.3892/ol.2017.6632
  • Pages: 3480-3486
  • Copyright: © Thompson et al. This is an open access article distributed under the terms of Creative Commons Attribution License.

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Abstract

Metformin is a biguanide employed in treating type II diabetes. Its potential efficacy for treating cancer has been demonstrated epidemiologically (lower cancer incidence in metformin users compared with users of sulfonylureas or insulin) and mechanistically, primarily in cell culture. Metformin decreases the levels of insulin‑like growth factor 1 and secondarily inhibits the mammalian target of rapamycin pathway to exhibit anticancer effects. The current study examined its cancer preventive efficacy in multiple standard in situ arising cancer models. Metformin was administered orally by gavage or in the diet, at human equivalent doses, in numerous cancer models. In the hydroxybutyl(butyl)nitrosamine‑induced model of invasive urinary bladder cancer, metformin (50 or 150 mg/kg body weight/day, intragastric) was ineffective despite high urinary concentrations of metformin. Metformin (250 or 500 ppm in diet) failed to decrease the incidence or invasiveness of squamous cell cancer of the tongue in a 4‑nitroquinoline‑1‑(4NQO)‑induced model. Finally, in the Min mouse model of gastrointestinal cancer, metformin (400 or 1,200 ppm in diet) was ineffective. Notably, a slight increase in intestinal tumor multiplicity was observed at the higher dose. Therefore, metformin lacked efficacy in multiple standard cancer models in non‑diabetic rodents. This lack of efficacy may discourage any large phase clinical cancer trials in non‑diabetic individuals in the absence of clear phase‑II studies.
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September-2017
Volume 14 Issue 3

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Spandidos Publications style
Thompson MD, Lubet RA, Mccormick DL, Clapper ML, Bode AM, Juliana MM, Moeinpour F and Grubbs CJ: Lack of chemopreventive efficacy of metformin in rodent models of urinary bladder, head and neck, and colon/intestine cancer. Oncol Lett 14: 3480-3486, 2017
APA
Thompson, M.D., Lubet, R.A., Mccormick, D.L., Clapper, M.L., Bode, A.M., Juliana, M.M. ... Grubbs, C.J. (2017). Lack of chemopreventive efficacy of metformin in rodent models of urinary bladder, head and neck, and colon/intestine cancer. Oncology Letters, 14, 3480-3486. https://doi.org/10.3892/ol.2017.6632
MLA
Thompson, M. D., Lubet, R. A., Mccormick, D. L., Clapper, M. L., Bode, A. M., Juliana, M. M., Moeinpour, F., Grubbs, C. J."Lack of chemopreventive efficacy of metformin in rodent models of urinary bladder, head and neck, and colon/intestine cancer". Oncology Letters 14.3 (2017): 3480-3486.
Chicago
Thompson, M. D., Lubet, R. A., Mccormick, D. L., Clapper, M. L., Bode, A. M., Juliana, M. M., Moeinpour, F., Grubbs, C. J."Lack of chemopreventive efficacy of metformin in rodent models of urinary bladder, head and neck, and colon/intestine cancer". Oncology Letters 14, no. 3 (2017): 3480-3486. https://doi.org/10.3892/ol.2017.6632