Vitamin D mitigates the adverse effects of obesity on breast cancer in mice.

摘要: Obesity is an established risk factor for postmenopausal breast cancer (BCa), insulin resistance, and vitamin D deficiency, all contribute to increased synthesis of mammary estrogens, the drivers estrogen receptor-positive (ER+) BCa growth. As both dietary calcitriol treatments inhibit signaling, we hypothesized that would be especially beneficial in mitigating adverse effects obesity on ER+BCa. To assess whether exerted growth compounds could reduce these unfavorable effects, employed a diet-induced (DIO) model ovariectomized C57BL/6 mice. Breast tumor cells originally from syngeneic Mmtv-Wnt1 transgenic mice were then implanted into fat pads lean obese DIO accelerated initiation progression tumors. Treatments with either or reduced causing delay appearance inhibiting continued Beneficial actions surrounding adipose tissue included repressed Esr1, aromatase, Cox2 expression; decreased tumor-derived PGE2; expression leptin receptors; adiponectin receptors. We demonstrate leptin, signaling also regulated LKB1/AMPK pathway contributing overall decrease local conclude D, acting by multiple interrelated pathways, mitigate obesity-enhanced setting.