Planta 9° Unidad de Investigación, Hospital Universitario Puerta del Mar, Avda. Ana de Viya 21, 11009 Cádiz, Spain.
Ann Hematol. 2012 Jan;91(1):83-8. doi: 10.1007/s00277-011-1246-8. Epub 2011 May 3.
Multiple myeloma (MM) is an incurable disease accompanied by low plasma levels of low-density lipoprotein cholesterol (LDL-c). The significance of altered cholesterol metabolism in the pathophysiology of MM remains elusive. Although it has been hypothesized that myeloma cells depend on exogenous cholesterol for its survival, the role of LDL-c on myeloma cells has not been elucidated. To evaluate the impact of exogenous LDL-c on cell viability, three human myeloma cell lines (RPMI-8226, NCI-H929, and U-266B1) were grown in the presence or absence of lipoproteins. Cell viability was markedly reduced in the absence of lipoproteins in sera. However, exogenous LDL-c improved cell viability. We showed that reduced cell viability was associated with increased levels of cleaved caspase-3, whereas proliferation rate remained unchanged. Interestingly, exogenous LDL-c counteracted apoptosis in human myeloma cell lines and primary cultures of human myeloma cells. Thus, our results demonstrated that LDL-c is an important anti-apoptotic factor for myeloma cells and begin to explain the hypocholesterolemia observed in patients with MM.
多发性骨髓瘤（MM）是一种无法治愈的疾病，伴有低密度脂蛋白胆固醇（LDL-c）的血浆水平降低。胆固醇代谢改变在 MM 病理生理学中的意义仍不清楚。尽管有人假设骨髓瘤细胞依赖外源性胆固醇生存，但 LDL-c 对骨髓瘤细胞的作用尚未阐明。为了评估外源性 LDL-c 对细胞活力的影响，在存在或不存在脂蛋白的情况下培养三种人骨髓瘤细胞系（RPMI-8226、NCI-H929 和 U-266B1）。在无脂蛋白的血清中，细胞活力明显降低。然而，外源性 LDL-c 提高了细胞活力。我们表明，细胞活力降低与裂解的 caspase-3 水平升高有关，而增殖率保持不变。有趣的是，外源性 LDL-c 逆转了人骨髓瘤细胞系和人骨髓瘤细胞原代培养物的细胞凋亡。因此，我们的结果表明，LDL-c 是人骨髓瘤细胞的重要抗凋亡因子，并开始解释 MM 患者观察到的低胆固醇血症。
