Research data on the influence of 25(OH)D3 and VK2 MK-7 vitamins

Multiple myeloma (MM) remains an incurable hematological malignancy. Bortezomib (BTZ) is a proteasome inhibitor widely used in MM therapy whose potent activity is often hampered by the development of resistance. The immune system is vital in the pathophysiology of BTZ resistance. Vitamins D (VD) and K (VK) modulate the immune system; therefore, they are potentially beneficial in MM. The aim of the study was to evaluate the effect of BTZ therapy and VD and VK supplementation on the proliferation potential and gene expression profiles of MM cells in terms of the development of BTZ resistance. The U266 MM cell line was incubated three times with BTZ, VD and VK at different timepoints. Then, proliferation assays, RNA sequencing and bioinformatics analysis were performed. We showed BTZ resistance to be mediated by processes related to ATP metabolism and oxidative phosphorylation. The upregulation of genes from the SNORDs family suggests the involvement of epigenetic mechanisms. Supplementation with VD and VK reduced the proliferation of MM cells in both the non-BTZ-resistant and BTZ-resistant phenotypes. VD and VK, by restoring proper metabolism, may have overcome resistance to BTZ in vitro. This observation forms the basis for further clinical trials evaluating VD and VK as potential adjuvant therapies for MM patients.

多发性骨髓瘤（Multiple Myeloma, MM）仍是一种无法治愈的血液系统恶性肿瘤。硼替佐米（Bortezomib, BTZ）是广泛应用于MM治疗的蛋白酶体抑制剂，但其强效抗肿瘤活性常因耐药性的产生而受到削弱。免疫系统在BTZ耐药的病理生理过程中具有关键作用。维生素D（VD）与维生素K（VK）可调控免疫系统功能，因此在MM治疗中具备潜在应用价值。本研究旨在评估BTZ单独治疗以及联合VD、VK补充干预，对MM细胞增殖潜能及BTZ耐药发生进程中基因表达谱的影响。研究将U266多发性骨髓瘤细胞系在不同时间点与BTZ、VD及VK共同孵育，实验重复三次。随后开展增殖实验、RNA测序（RNA Sequencing）及生物信息学分析。结果显示，BTZ耐药性的产生与ATP代谢、氧化磷酸化相关生物学过程密切相关；SNORDs家族基因的上调提示表观遗传机制参与了耐药调控。VD与VK补充干预可分别降低非BTZ耐药型及BTZ耐药型MM细胞的增殖能力。VD与VK可通过恢复正常细胞代谢过程，在体外逆转BTZ耐药。该研究结果为后续开展VD、VK作为MM患者潜在辅助治疗方案的临床试验奠定了基础。