UNASSIGNED: Male ApoE-/- mice were fed with a HFD or a normal diet (ND) for 15 weeks. On the first day of Week 13, the mice were inoculated subcutaneously in the right axilla with Lewis lung cancer cells. At Weeks 12 and 15, serum lectin-like oxidized low-density lipoprotein receptor-1 (LOX-1) and vascular endothelial growth factor levels were measured by enzyme-linked immunosorbent assay, and blood monocytes and macrophages were measured by fluorescence-activated cell sorting. At Week 15, the volume and weight of the local subcutaneous lung cancer and metastatic lung cancer and the amount of aortic atherosclerosis were measured.
UNASSIGNED: At Week 15, compared with mice in the ND group, those in the HFD group had a larger volume of local subcutaneous cancer (p = 0.0004), heavier tumors (p = 0.0235), more metastatic cancer in the lungs (p < 0.0001), a larger area of lung involved in metastatic cancer (p = 0.0031), and larger areas of atherosclerosis in the aorta (p < 0.0001). At Week 12, serum LOX-1, serum vascular endothelial growth factor, and proportions of blood monocytes and macrophages were significantly higher in the HFD group than those in the ND group (p = 0.0002, p = 0.0029, p = 0.0480, and p = 0.0106, respectively); this trend persisted until Week 15 (p = 0.0014, p = 0.0012, p = 0.0001, and p = 0.0204).
UNASSIGNED: In this study, HFD-induced obesity could simultaneously promote progression of lung cancer and atherosclerosis in the same mouse. HFD-induced upregulation of LOX-1 may play an important role in the simultaneous progression of these two conditions via the inflammatory response and VEGF.
■用HFD或正常饮食(ND)喂养雄性ApoE-/-小鼠15周。在第13周的第一天,小鼠在右腋下皮下接种Lewis肺癌细胞。在第12周和第15周,通过酶联免疫吸附试验测量血清凝集素样氧化低密度脂蛋白受体-1(LOX-1)和血管内皮生长因子水平,通过荧光激活细胞分选测量血液单核细胞和巨噬细胞。在第15周,测量局部皮下肺癌和转移性肺癌的体积和重量以及主动脉粥样硬化的量。
■在第15周,与ND组的小鼠相比,HFD组的局部皮下癌体积较大(p=0.0004),肿瘤较重(p=0.0235),肺部转移癌更多(p<0.0001),更大的肺面积参与转移癌(p=0.0031),主动脉动脉粥样硬化面积较大(p<0.0001)。在第12周,血清LOX-1,血清血管内皮生长因子,HFD组的单核细胞和巨噬细胞的比例明显高于ND组(分别为p=0.0002,p=0.0029,p=0.0480和p=0.0106);这种趋势持续到第15周(p=0.0014,p=0.0012,p=0.0001和p=0.0204)。
■在这项研究中,HFD诱导的肥胖可同时促进同一小鼠肺癌和动脉粥样硬化的进展。HFD诱导的LOX-1上调可能通过炎症反应和VEGF在这两种疾病的同时进展中起重要作用。