A high energy balance, or caloric excess, accounts as a
tumor promoting factor, while a negative energy balance via
caloric restriction, has been shown to delay
cancer progression. The effect of energy balance on
ovarian cancer progression was investigated in an isogeneic immunocompetent mouse model of
epithelial ovarian cancer kept on a regimen of regular diet, high energy diet (HED) and
calorie restricted diet (CRD), prior to inoculating the animals intraperitoneally with the mouse ovarian surface epithelial ID8
cancer cells.
Tumor evaluation revealed that mice group on HED displayed the most extensive
tumor formation with the highest
tumor score at all organ sites (diaphragm, peritoneum, bowel, liver, kidney, spleen), accompanied with increased levels of
insulin,
leptin,
insulin growth factor-1 (IGF-1),
monocyte chemoattractant protein-1 (MCP-1),
VEGF and
interleukin 6 (IL-6). On the other hand, the mice group on CRD exhibited the least
tumor burden associated with a significant reduction in levels of
insulin,
IGF-1,
leptin, MCP-1,
VEGF and
IL-6. Immunohistochemistry analysis of
tumors from HED mice showed higher activation of Akt and mTOR with decreased
adenosine monophosphate activated
kinase (AMPK) and
SIRT1 activation, while
tumors from the CRD group exhibited the reverse profile. In conclusion,
ovarian cancer growth and
metastasis occurred more aggressively under HED conditions and was significantly curtailed under CRD. The suggested mechanism involves modulated secretion of
growth factors,
cytokines and altered regulation of AMPK and
SIRT1 that converges on mTOR inhibition. While the role of a high energy state in
ovarian cancer has not been confirnmed in the literature, the current findings support investigating the potential impact of diet modulation as adjunct to other anticancer
therapies and as possible individualized treatment strategy of
epithelial ovarian cancer.