PDF(Pubmed)
Abstract：
Young women have increased risk of vitamin D deficiency, which may increase breast cancer incidence. Here, we assessed the anti-cancer efficacy of vitamin D in mouse models of young-onset breast cancer. In never-pregnant mice, vitamin D supplementation increased serum 25(OH)D and hepatic 1,25(OH)2D3, reduced tumor size, and associated with anti-tumor immunity. These anti-tumor effects were not replicated in a mouse model of postpartum breast cancer, where hepatic metabolism of vitamin D was suppressed post-wean, which resulted in deficient serum 25(OH)D and reduced hepatic 1,25(OH)2D3. Treatment with active 1,25(OH)2D3 induced hypercalcemia exclusively in post-wean mice, highlighting metabolic imbalance post-wean. RNAseq revealed suppressed CYP450 expression postpartum. In sum, we provide evidence that vitamin D anti-tumor activity is mediated through immunomodulatory mechanisms and is ineffective in the post-wean window due to altered hepatic metabolism. These findings have implications for suppressed xenobiotic metabolism in postpartum women beyond vitamin D.
摘要：
年轻女性维生素D缺乏的风险增加，这可能会增加乳腺癌的发病率。这里,我们评估了维生素D在幼发乳腺癌小鼠模型中的抗癌功效.在从未怀孕的老鼠中，补充维生素D可增加血清25（OH）D和肝脏1,25（OH）2D3，减小肿瘤大小，并与抗肿瘤免疫有关。这些抗肿瘤作用在产后乳腺癌小鼠模型中没有复制，断奶后维生素D的肝脏代谢受到抑制，导致血清25(OH)D缺乏，肝脏1,25(OH)2D3减少。用活性1,25(OH)2D3治疗仅在断奶后小鼠中诱导高钙血症，强调断奶后代谢失衡。RNAseq显示产后CYP450表达受抑制。总之,我们提供的证据表明，维生素D抗肿瘤活性是通过免疫调节机制介导的，并且由于肝脏代谢改变，在断奶后窗口无效。这些发现对产后妇女体内抑制的外源性生物代谢具有意义，超过维生素D。
■在产后乳腺癌的啮齿动物模型中，断奶抑制肝脏CYP450活性，使补充维生素D无效，对异种生物药物的疗效和安全性有影响。根据生育史量身定制的治疗方法对年轻乳腺癌患者至关重要，以及产后妇女的保健策略。
■在产后乳腺癌的啮齿动物模型中，断奶抑制肝脏CYP450活性，使补充维生素D无效，对异种生物药物的疗效和安全性有影响。根据生育史量身定制的治疗方法对年轻乳腺癌患者至关重要，以及产后妇女的保健策略。
