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. 2015 Mar 26;6(13):10908–10923. doi: 10.18632/oncotarget.3434

Figure 8. Proposed mechanism of metformin effect on ovarian cancer.

Figure 8

Metformin and CR act in a similar manner to curtail ovarian cancer growth, while HED aggravates ovarian cancer. Both metformin and CR result in activation of AMPK and SIRT1. SIRT1 activation could occur independently or as a consequence of AMPK activation. Activation of these metabolic enzymes is linked to reduction in growth factors and hormones like insulin, IGF-1 and leptin, which leads to inhibition in the protein kinase B-mammalian target of rapamycin (Akt-mTOR) pathway activation resulting in decreased ovarian tumor growth. Inhibition of cytokines like MCP-1 and IL-6 and the angiogenic factor VEGF reduces inflammation and angiogenesis, which also leads to limited ovarian tumor growth. Overall, metformin and CR have very similar effects in modulating the deranged tumor environment milieu and in effect restricts ovarian cancer progression. AMPK, adenosine monophosphate activated kinase; CR, caloric restriction; HED, high energy diet; IGF-1, insulin growth factor 1; IL-6, interleukin 6; MCP-1, monocyte chemoattractant protein-1; SIRT1, sirtuin 1; VEGF, vascular endothelial growth factor.