Fixed-Dose combinations of pioglitazone & metformin for lung cancer prevention

Donna E. Seabloom, Arthur R. Galbraith, Anna M. Haynes, Jennifer D. Antonides, Beverly RWuertz, Wendy A. Miller, Kimberly A. Miller, Vernon E. Steele, Mark Steven Miller, Margie L. Clapper, M. Gerard O'sullivan, Frank G. Ondrey

Research output: Contribution to journalArticlepeer-review

15 Scopus citations

Abstract

Combination treatment with pioglitazone and metformin is utilized clinically in the treatment of type II diabetes. Treatment with this drug combination reduced the development of aerodigestive cancers in this patient population. Our goal is to expand this treatment into clinical lung cancer chemoprevention. We hypothesized that dietary delivery of metformin/pioglitazone would prevent lung adenoma formation in A/J mice in a benzo[ a]pyrene (B[a]P)-induced carcinogenesis model while modulating chemoprevention and anti-inflammatory biomarkers in residual adenomas. We found that metformin (500 and 850 mg/kg/d) and pioglitazone (15 mg/kg/d) produced statistically significant decreases in lung adenoma formation both as singleagent treatments and in combination, compared with untreated controls, after 15 weeks. Treatment with metformin alone and in combination with pioglitazone resulted in statistically significant decreases in lung adenoma formation at both early-And late-stage interventions. Pioglitazone alone resulted in significant decreases in adenoma formation only at early treatment intervention. We conclude that oral metformin is a viable chemopreventive treatment at doses ranging from 500 to 1,000 mg/kg/d. Pioglitazone at 15 mg/kg/d is a viable chemopreventive agent at earlystage interventions. Combination metformin and pioglitazone performed equal to metformin alone and better than pioglitazone at 15 mg/kg/d. Because the drugs are already FDAapproved, rapid movement to human clinical studies is possible.

Original languageEnglish (US)
Pages (from-to)116-123
Number of pages8
JournalCancer Prevention Research
Volume10
Issue number2
DOIs
StatePublished - Feb 2017

Bibliographical note

Funding Information:
This work was supported by the NCI (Subcontract for Preclinical ContractN01CN25002- 78, Primary Contract Number: Contract #HHSN- 261201200015I, F.G. Ondrey) and the Lions Multiple District 5M Hearing Foundation of Minnesota, (Translational Biomarker Initiatives for Medical Students, F.G. Ondrey).

Publisher Copyright:
©2016 American Association for Cancer Research.

Copyright:
Copyright 2017 Elsevier B.V., All rights reserved.

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