Metformin suppresses intestinal polyp growth in Apc Min/+ mice

Tomimoto, Ayako; Endo, Hiroki; Sugiyama, Michiko; Fujisawa, Toshio; Hosono, Kunihiro; Takahashi, Hirokazu; Nakajima, Noriko; Nagashima, Yoji; Wada, Koichiro; Nakagama, Hitoshi; Nakajima, Atsushi

doi:10.1111/j.1349-7006.2008.00933.x

Cited by 186Metabolism, Diabetes, and CancerPI3K/AKT/mTOR signaling in cancerColorectal Cancer Treatments and Studies

Metformin suppresses intestinal polyp growth in Apc Min/+ mice

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Tomimoto, Ayako, Endo, Hiroki, Sugiyama, Michiko, Fujisawa, Toshio, Hosono, Kunihiro, Takahashi, Hirokazu, Nakajima, Noriko, Nagashima, Yoji +3 more·2008·Cancer Science

DOI 10.1111/j.1349-7006.2008.00933.xPMC PMC11159964

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Abstract

Metformin is a biguanide derivative that is widely used in the treatment of diabetes mellitus. One of the pharmacological targets of metformin is adenosine monophosphate-activated protein kinase (AMPK). We investigated the effect of metformin on the suppression of intestinal polyp formation in Apc(Min/+) mice. Administration of metformin (250 mg/kg) did not reduce the total number of intestinal polyp formations, but significantly reduced the number of intestinal polyp formations larger than 2 mm in diameter in Apc(Min/+) mice. To examine the indirect effect of metformin, the index of insulin resistance and serum lipid levels in Apc(Min/+) mice were assessed. These factors were not significantly attenuated by the treatment with metformin, indicating that the suppression of polyp growth is not due to the indirect drug action. The levels of tumor cell proliferation as determined by 5-bromodeoxyuridine and proliferating cell nuclear antigen immunohistochemical staining, and apoptosis, via transferase deoxytidyl uridine end labeling staining, in the polyps of metformin-treated mice were not significantly different in comparison to those of control mice. Gene expression of cyclin D1 and c-myc in intestinal polyps were also not significantly different between those two groups. In contrast, metformin activated AMPK in the intestinal polyps, resulting in the inhibition of the activation of mammalian target of rapamycin, which play important roles in the protein synthesis machinery. Metformin suppressed the polyp growth in Apc(Min/+) mice, suggesting that it may be a novel candidate as a chemopreventive agent for colorectal cancer.

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From Metformin, the Aspirin of the 21st Century: Its Role in Gestational Diabetes Mellitus, Prevention of Preeclampsia and Cancer, and the Promotion of Longevity (2017) · cites this paper as [263]

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Retracted
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Metformin suppresses azoxymethane‐induced colorectal aberrant crypt foci by activating AMP‐activated protein kinase
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Abstract 5111: Metformin suppresses azoxymethane-induced colorectal carcinogenesis via activating AMP-activated protein kinase
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Self-citation
Metformin efficacy and safety for colorectal polyps: a double-blind randomized controlled trial
Higurashi, T., Takahashi, H., Endo, H., Hosono, K., Yamada, E., Ohkubo, H., Sakai, E., Uchiyama, T., Hata, Y., Fujisawa, N., et al. (2012) · BMC Cancer · doi:10.1186/1471-2407-12-118 · Cited by 55 · see citing works
Self-citation
Adiponectin suppresses tumorigenesis in ApcMin/+ mice
Otani, K., Kitayama, J., Yasuda, K., Nio, Y., Iwabu, M., Okudaira, S., Aoki, J., Yamauchi, T., Kadowaki, T., & Nagawa, H. (2009) · Cancer Letters · doi:10.1016/j.canlet.2009.06.037 · Cited by 49 · see citing works
Loss of Adiponectin Promotes Intestinal Carcinogenesis in Min and Wild-type Mice
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Authors: Tomimoto, A., Endo, H., Sugiyama, M., Fujisawa, T., Hosono, K., Takahashi, H., Nakajima, N., Nagashima, Y., Wada, K., Nakagama, H., & Nakajima, A.
Affiliations: National Institute of Infectious Diseases (JP)
Yokohama City University (JP)
The University of Osaka (JP)
National Cancer Center Research Institute (JP)
Corresponding author: Nakajima, Atsushi
ORCID: Fujisawa, Toshio
Hosono, Kunihiro
Takahashi, Hirokazu
Nakajima, Noriko
Nagashima, Yoji
Wada, Koichiro
Nakajima, Atsushi
Venue: Cancer Science
Publisher: Wiley
Published: 2008-11
Volume: 99
Issue: 11
Pages: 2136-2141
ISSN: 1347-9032 (ISSN-L)
1349-7006
DOI: 10.1111/j.1349-7006.2008.00933.x
PMC: PMC11159964
OpenAlex: W2140983197
Cited by: 185
References: 24
Citations by year: 2026: 2 · 2025: 4 · 2024: 9 · 2023: 5 · 2022: 9 · 2021: 7 · 2020: 8 · 2019: 9 · 2018: 10 · 2017: 9 · 2016: 6 · 2015: 15 · 2014: 20 · 2013: 16 · 2012: 22
FWCI: 4.67
Type: journal article
Language: en
Open access: bronze
doi.org
Licence: onlinelibrary.wiley.com/termsAndConditions#vor (vor)
Locations: Cancer Science (publishedVersion)
PubMed Central (publishedVersion)
PubMed (publishedVersion)
Funders: National Institute of Biomedical Innovation
Princess Takamatsu Cancer Research Fund
Topics: Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Metabolism, Diabetes, and Cancer
Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › PI3K/AKT/mTOR signaling in cancer
Health Sciences › Medicine › Oncology › Colorectal Cancer Treatments and Studies
Keywords: metformin, intestinal polyps, ApcMin/+ mice, AMPK, mTOR, colorectal cancer chemoprevention, insulin resistance, serum lipids, tumor cell proliferation, apoptosis, cyclin D1, c-Myc
MeSH terms: Animals, Immunohistochemistry, Intestinal Polyps, Metformin, Mice, Inbred C57BL, Mice, Transgenic, Gene Expression Regulation, Neoplastic, Proto-Oncogene Proteins c-myc, Anticarcinogenic Agents, Genes, APC, Cyclin D1, Cell Proliferation, Mice

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Metformin suppresses intestinal polyp growth in Apc Min/+ mice

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