Cellular lipid metabolism, lipoprotein interactions, and liver X receptor (LXR) activation have been implicated in the pathophysiology and treatment of cancer, although findings vary across cancer models and by lipoprotein profiles. In this study, we investigated the effects of human‐derived low‐density lipoproteins (LDL), high‐density lipoproteins (HDL), and HDL‐associated proteins apolipoprotein A1 (apoA1) and serum amyloid A (SAA) on markers of viability, cholesterol flux, and differentiation in K562 cells—a bone marrow‐derived, stem‐like erythroleukemia cell model of chronic myelogenous leukemia (CML). We further evaluated whether lipoprotein‐mediated effects were altered by concomitant LXR activation. We observed that LDL promoted higher K562 cell viability in a dose‐ and time‐dependent manner and increased cellular cholesterol concentrations, while LXR activation by the agonist TO901317 ablated these effects. LXR activation in the presence of HDL, apoA1 and SAA‐rich HDL suppressed K562 cell viability, while robustly inducing mRNA expression of ATP‐binding cassette transporter A1 (ABCA1). HDL and its associated proteins additionally suppressed mRNA expression of anti‐apoptotic B‐cell lymphoma‐extra large (BCL‐xL), and the erythroid lineage marker 5′‐aminolevulinate synthase 2 (ALAS2), while SAA‐rich HDL induced mRNA expression of the megakaryocytic lineage marker integrin subunit alpha 2b (ITGA2B). Together, these findings suggest that lipoproteins and LXR may impact the viability and characteristics of CML cells.

中文翻译：

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低密度脂蛋白、高密度脂蛋白 (HDL) 和 HDL 相关蛋白差异调节慢性粒细胞白血病细胞活力。

细胞脂质代谢、脂蛋白相互作用和肝 X 受体 (LXR) 激活与癌症的病理生理学和治疗有关，尽管研究结果因癌症模型和脂蛋白谱而异。在这项研究中，我们研究了人源性低密度脂蛋白 (LDL)、高密度脂蛋白 (HDL) 和 HDL 相关蛋白载脂蛋白 A1 (apoA1) 和血清淀粉样蛋白 A (SAA) 对生存能力标志物的影响，胆固醇通量和 K562 细胞的分化——一种骨髓来源的、慢性粒细胞白血病 (CML) 的干细胞样红白血病细胞模型。我们进一步评估了脂蛋白介导的作用是否因伴随的 LXR 激活而改变。我们观察到 LDL 以剂量和时间依赖性方式促进更高的 K562 细胞活力，并增加细胞胆固醇浓度，而激动剂 TO901317 的 LXR 激活消除了这些影响。在 HDL、apoA1 和富含 SAA 的 HDL 存在下，LXR 激活抑制 K562 细胞活力，同时强力诱导 ATP 结合盒转运蛋白 A1 的 mRNA 表达。ABCA1 )。HDL 及其相关蛋白还抑制了抗凋亡 B 细胞淋巴瘤超大 ( BCL-xL)和红细胞谱系标记物 5'-氨基乙酰丙酸合酶 2 ( ALAS2 ) 的 mRNA 表达，而富含 SAA 的 HDL 诱导了巨核细胞谱系标记整合素亚基 α 2b ( ITGA2B )。总之，这些发现表明脂蛋白和 LXR 可能影响 CML 细胞的活力和特征。