Kamiya Sakura, Nakamori Yuna, Takasawa Akira, Takasawa Kumi, Kyuno Daisuke, Ono Yusuke, Magara Kazufumi, Osanai Makoto
Department of Pathology, Sapporo Medical University School of Medicine, Sapporo 060-0061, Japan.
Oncol Rep. 2023 May;49(5). doi: 10.3892/or.2023.8522. Epub 2023 Mar 17.
Vitamin D is an essential nutrient for the human body not only for the metabolism of calcium but also for homeostasis. Vitamin D contributes to cell fate decisions, including cell proliferation, differentiation and viability. Accumulated epidemiological data suggest a relationship between vitamin D deficiency and carcinogenesis in numerous organs. Furthermore, it is known that the expression of the vitamin D metabolizing enzyme, cytochrome P450 family 24 subtype A1 (CYP24A1), is increased in different types of human malignancy including breast carcinoma. However, the pathological relevance of elevated CYP24A1 expression level requires further clarification. In the present study, it was demonstrated that CYP24A1 promoted the oncogenic property of breast carcinoma cells. Consistent with previous reports, it was demonstrated that the expression of CYP24A1 was elevated in invasive breast carcinoma and significantly decreased the overall survival of patients with invasive breast carcinoma. Importantly, suppression of CYP24A1 expression significantly enhanced cell death sensitivity to two anticancer drugs with pharmacologically different modes of action, cisplatin and gefitinib. The results of the present study suggest the possibility of CYP24A1‑inhibiting therapy as a novel therapy in breast cancer with overexpression of CYP24A1.
维生素D是人体必需的营养素，不仅对钙的代谢至关重要，而且对体内平衡也很重要。维生素D有助于细胞命运的决定，包括细胞增殖、分化和活力。大量流行病学数据表明维生素D缺乏与许多器官的致癌作用之间存在关联。此外，已知维生素D代谢酶细胞色素P450家族24亚家族A1（CYP24A1）在包括乳腺癌在内的不同类型人类恶性肿瘤中的表达会增加。然而，CYP24A1表达水平升高的病理相关性需要进一步阐明。在本研究中，证明了CYP24A1促进了乳腺癌细胞的致癌特性。与先前的报道一致，证明CYP24A1在浸润性乳腺癌中的表达升高，并显著降低了浸润性乳腺癌患者的总生存率。重要的是，抑制CYP24A1表达显著增强了对两种具有不同药理作用模式的抗癌药物顺铂和吉非替尼的细胞死亡敏感性。本研究结果提示，对于CYP24A1过表达的乳腺癌，CYP24A1抑制疗法有可能成为一种新的治疗方法。
