Visualizing the effects of metformin on tumor growth, vascularity and metabolism in head and neck cancer.

Visualizing the effects of metformin on tumor growth, vascularity and metabolism in head and neck cancer.

J Oral Pathol Med. 2018 Mar 23;:

Authors: Verma A, Rich LJ, Vui King VC, Seshadri M

Abstract
BACKGROUND: The anti-diabetic drug Metformin (Met) is believed to inhibit tumor proliferation by altering the metabolism of cancer cells. In this study, we examined the effects of on tumor oxygenation, metabolism and growth in head and neck squamous cell carcinoma (HNSCC) using non-invasive multimodal imaging MATERIALS AND METHODS: Severe combined immunodeficient (SCID) mice bearing orthotopic FaDu HNSCC xenografts were treated with Met (200 mg/kg, i.p.) once daily for 5 days. Tumor oxygen saturation (%sO2 ) and hemoglobin concentration (HbT) were measured using photoacoustic imaging (PAI). Fluorescence imaging was employed to measure intratumoral uptake of 2-deoxyglucosone (2-DG) following Met treatment while magnetic resonance imaging (MRI) was utilized to measure tumor volume. Correlative immunostaining of tumor sections for markers of proliferation (Ki67) and vascularity (CD31) was also performed.
RESULTS: At 5 days post Met treatment, PAI revealed a significant increase (p<0.05) in %sO2 and HbT levels in treated tumors compared to untreated controls. Fluorescence imaging at this time point revealed a 46% decrease in mean 2-DG uptake compared to controls. No changes in hemodynamic parameters were observed in mouse salivary gland tissue. A significant decrease in Ki-67 staining (p<0.001) and MR-based tumor volume was also observed in Met-treated tumors compared to controls with no change in CD31+ vessel count following Met therapy.
CONCLUSION: Our results provide, for the first time, direct in vivo evidence of Met-induced changes in tumor microenvironmental parameters in HNSCC xenografts. Our findings highlight the utility of multimodal functional imaging for non-invasive mapping of the effects of Met in HNSCC. This article is protected by copyright. All rights reserved.

PMID: 29573032 [PubMed - as supplied by publisher]

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