Gkotinakou Ioanna-Maria, Mylonis Ilias, Tsakalof Andreas
Laboratory of Biochemistry, Faculty of Medicine, University of Thessaly, Biopolis, 41500 Larissa, Greece.
Cancers (Basel). 2022 Mar 31;14(7):1791. doi: 10.3390/cancers14071791.
Vitamin D is a hormone that, through its action, elicits a broad spectrum of physiological responses ranging from classic to nonclassical actions such as bone morphogenesis and immune function. In parallel, many studies describe the antiproliferative, proapoptotic, antiangiogenic effects of calcitriol (the active hormonal form) that contribute to its anticancer activity. Additionally, epidemiological data signify the inverse correlation between vitamin D levels and cancer risk. On the contrary, tumors possess several adaptive mechanisms that enable them to evade the anticancer effects of calcitriol. Such maladaptive processes are often a characteristic of the cancer microenvironment, which in solid tumors is frequently hypoxic and elicits the overexpression of Hypoxia-Inducible Factors (HIFs). HIF-mediated signaling not only contributes to cancer cell survival and proliferation but also confers resistance to anticancer agents. Taking into consideration that calcitriol intertwines with signaling events elicited by the hypoxic status cells, this review examines their interplay in cellular signaling to give the opportunity to better understand their relationship in cancer development and their prospect for the treatment of cancer.
维生素D是一种激素，通过其作用引发从经典到非经典作用的广泛生理反应，如骨形态发生和免疫功能。同时，许多研究描述了骨化三醇（活性激素形式）的抗增殖、促凋亡、抗血管生成作用，这些作用有助于其抗癌活性。此外，流行病学数据表明维生素D水平与癌症风险呈负相关。相反，肿瘤具有多种适应性机制，使其能够逃避骨化三醇的抗癌作用。这种适应不良过程通常是癌症微环境的一个特征，在实体瘤中，微环境常常缺氧并引发缺氧诱导因子（HIFs）的过度表达。HIF介导的信号传导不仅有助于癌细胞的存活和增殖，还赋予对抗癌药物的抗性。考虑到骨化三醇与缺氧状态细胞引发的信号事件相互交织，本综述研究了它们在细胞信号传导中的相互作用，以便更好地理解它们在癌症发展中的关系以及癌症治疗前景。
