Dataset Information

SGLT2 inhibition slows tumor growth in mice by reversing hyperinsulinemia.

ABSTRACT:

Background

Obesity confers an increased risk and accelerates the progression of multiple tumor types in rodents and humans, including both breast and colon cancer. Because sustained weight loss is rarely achieved, therapeutic approaches to slow or prevent obesity-associated cancer development have been limited, and mechanistic insights as to the obesity-cancer connection have been lacking.

Methods

E0771 breast tumors and MC38 colon tumors were treated in vivo in mice and in vitro with two mechanistically different insulin-lowering agents, a controlled-release mitochondrial protonophore (CRMP) and sodium-glucose cotransporter-2 (SGLT2) inhibitors, and tumor growth and glucose metabolism were assessed. Groups were compared by ANOVA with Bonferroni's multiple comparisons test.

Results

Dapagliflozin slows tumor growth in two mouse models (E0771 breast cancer and MC38 colon adenocarcinoma) of obesity-associated cancers in vivo, and a mechanistically different insulin-lowering agent, CRMP, also slowed breast tumor growth through its effect to reverse hyperinsulinemia. In both models and with both agents, tumor glucose uptake and oxidation were not constitutively high, but were hormone-responsive. Restoration of hyperinsulinemia by subcutaneous insulin infusion abrogated the effects of both dapagliflozin and CRMP to slow tumor growth.

Conclusions

Taken together, these data demonstrate that hyperinsulinemia per se promotes both breast and colon cancer progression in obese mice, and highlight SGLT2 inhibitors as a clinically available means of slowing obesity-associated tumor growth due to their glucose- and insulin-lowering effects.

SUBMITTER: Nasiri AR

PROVIDER: S-EPMC6907191 | biostudies-literature | 2019

REPOSITORIES: biostudies-literature

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Publications

SGLT2 inhibition slows tumor growth in mice by reversing hyperinsulinemia.

Nasiri Ali R AR Rodrigues Marcos R MR Li Zongyu Z Leitner Brooks P BP Perry Rachel J RJ

Cancer & metabolism 20191211

<h4>Background</h4>Obesity confers an increased risk and accelerates the progression of multiple tumor types in rodents and humans, including both breast and colon cancer. Because sustained weight loss is rarely achieved, therapeutic approaches to slow or prevent obesity-associated cancer development have been limited, and mechanistic insights as to the obesity-cancer connection have been lacking.<h4>Methods</h4>E0771 breast tumors and MC38 colon tumors were treated in vivo in mice and in vitro ...[more]

PMID: 31867105

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Dataset Information

SGLT2 inhibition slows tumor growth in mice by reversing hyperinsulinemia.

Background

Methods

Results

Conclusions

Publications

SGLT2 inhibition slows tumor growth in mice by reversing hyperinsulinemia.

Similar Datasets

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