Abu El Maaty Mohamed A, Wölfl Stefan
Institut für Pharmazie und Molekulare Biotechnologie (IPMB), Universität Heidelberg, Im Neuenheimer Feld 364, 69120 Heidelberg, Germany.
Nutrients. 2017 Jan 23;9(1):87. doi: 10.3390/nu9010087.
The diverse effects of 1,25-dihydroxyvitamin D₃ (1,25(OH)₂D₃), the bio-active form of vitamin D, on cancer cell metabolism and proliferation has made it an interesting candidate as a supporting therapeutic option in cancer treatment. An important strategy in cancer therapy is the use of combination chemotherapy to overcome drug resistance associated with numerous anti-cancer agents and to provide better means of avoiding undesirable side effects. This complex strategy is widely adopted by oncologists and several established "cocktails" of chemotherapeutics are routinely administered to cancer patients. Among the principles followed in designing such treatment regimens is the use of drugs with different mechanisms of action to overcome the issue of tumor heterogeneity and to evade resistance. In light of the profound and diverse effects of 1,25(OH)₂D₃ reported by in vitro and in vivo studies, we discuss how these effects could support the use of this molecule in combination with "classical" cytotoxic drugs, such as platins and anti-metabolites, for the treatment of solid and hematological tumors. We also examine recent evidence supporting synergistic activities with other promising anti-cancer drug candidates, and postulate mechanisms through which 1,25(OH)₂D₃ may help evade chemoresistance.
维生素D的生物活性形式1,25-二羟基维生素D₃（1,25(OH)₂D₃）对癌细胞代谢和增殖具有多种作用，这使其成为癌症治疗中一种有吸引力的辅助治疗选择。癌症治疗的一个重要策略是联合化疗，以克服与多种抗癌药物相关的耐药性，并提供更好的方法来避免不良副作用。这种复杂的策略被肿瘤学家广泛采用，几种成熟的化疗“鸡尾酒”方案被常规用于癌症患者。设计此类治疗方案所遵循的原则之一是使用具有不同作用机制的药物，以克服肿瘤异质性问题并规避耐药性。鉴于体外和体内研究报道的1,25(OH)₂D₃的深远和多样作用，我们讨论了这些作用如何支持将该分子与“经典”细胞毒性药物（如铂类和抗代谢物）联合用于实体瘤和血液肿瘤的治疗。我们还研究了支持与其他有前景的抗癌候选药物协同活性的最新证据，并推测了1,25(OH)₂D₃可能有助于规避化疗耐药性的机制。
