Department of Clinical Nutrition, Shengjing Hospital of China Medical University, Shenyang 110004, China.
Children's Neurorehabilitation Laboratory, Shenyang Children's Hospital, Shenyang 110032, China.
J Adv Res. 2020 Aug 27;29:13-22. doi: 10.1016/j.jare.2020.08.013. eCollection 2021 Mar.
Intrinsic vitamin D affects the proliferation, apoptosis, invasion, metastasis, and tumorigenesis of lung cancer by regulating tumor signaling pathways. Histidine-rich calcium-binding protein (HRC) maintains Ca homeostasis, which plays crucial roles in the occurrence and development of cancer.
Our study aims to investigate the ability of vitamin D in the regulation of HRC and the role of HRC playing in lung cancer.
We investigated the effects of vitamin D on lung cancer and the underlying mechanisms, by measuring HRC and vitamin D receptor (VDR) expression in lung cancer, paracancer, and normal tissues from patients using immunohistochemistry, western blotting, and real time RT-PCR. We transfected H460 lung cancer cells (supplemented or not with vitamin D) with PX458-HRC and pcDNA3.1-HRC plasmids and injected mice with lung cancer cells harboring pcDNA3.1-vector or pcDNA3.1-HRC plasmids.
Vitamin D inhibited HRC expression and H460 cell migration and proliferation, and promoted apoptosis compared with controls. The expression of HRC and VDR was significantly upregulated and downregulated, respectively, in lung cancer versus paracancer or normal tissues. Cell proliferation and migration were reduced, apoptotic cells were more and tumors were smaller in mice treated with vitamin D/cholecalciferol cholesterol emulsion (CCE) than in vitamin D/CCE+HRC mice.
Vitamin D inhibited lung cancer tumor growth, migration, and proliferation by downregulating HRC.
内源性维生素 D 通过调节肿瘤信号通路影响肺癌的增殖、凋亡、侵袭、转移和发生。富含组氨酸的钙结合蛋白（HRC）维持钙稳态，在癌症的发生和发展中发挥着关键作用。
本研究旨在探讨维生素 D 调节 HRC 的能力以及 HRC 在肺癌中的作用。
我们通过免疫组织化学、Western blot 和实时 RT-PCR 检测了患者肺癌、癌旁组织和正常组织中 HRC 和维生素 D 受体（VDR）的表达，来研究维生素 D 对肺癌的影响及其潜在机制。我们用 PX458-HRC 和 pcDNA3.1-HRC 质粒转染 H460 肺癌细胞（补充或不补充维生素 D），并将携带有 pcDNA3.1-载体或 pcDNA3.1-HRC 质粒的肺癌细胞注射到小鼠体内。
与对照组相比，维生素 D 抑制了 HRC 的表达以及 H460 细胞的迁移和增殖，并促进了细胞凋亡。与癌旁或正常组织相比，肺癌组织中 HRC 和 VDR 的表达分别显著上调和下调。与维生素 D/胆钙化醇胆固醇乳剂（CCE）处理组相比，维生素 D/CCE+HRC 处理组的细胞增殖和迁移减少，凋亡细胞增多，肿瘤体积减小。
维生素 D 通过下调 HRC 抑制肺癌肿瘤生长、迁移和增殖。
