Department of Internal Medicine, Affiliated Guangzhou Women and Children's Medical Center, Sun Yat‑sen University, Guangzhou, Guangdong 510080, P.R. China.
Department of Biochemistry, Zhongshan School of Medicine, Sun Yat‑sen University, Guangzhou, Guangdong 510080, P.R. China.
Int J Oncol. 2019 Feb;54(2):572-584. doi: 10.3892/ijo.2018.4648. Epub 2018 Nov 26.
Gastric cancer is one of the most malignant tumor types, and its metastasis is a notable cause of mortality. Among the methods of tumor metastasis, lymphatic metastasis is the predominant one in gastric cancer. A previous study reported that the plasma oxidized low‑density lipoprotein (oxLDL) is the risk factor associated with the development of tumors in patients with abnormal lipid metabolism, but the influence of plasma oxLDL in the lymphatic metastasis of gastric cancer remains unclear. In the present study, the concentration of plasma oxLDL from patients with gastric cancer was detected with an ELISA kit, and the lymphatic vessel density in gastric cancer tissues was determined by D2‑40 staining. The correlation analysis of oxLDL concentration and lymphatic vessel density demonstrated that plasma oxLDL was positively correlated with lymphatic metastasis in patients with gastric cancer. Subsequently, the popliteal lymph node metastasis animal experiment with nude mice confirmed that oxLDL could promote the lymphatic metastasis of gastric cancer. Following this, the western blotting and ELISA data demonstrated that oxLDL promoted the expression and secretion of vascular endothelia growth factor (VEGF)‑C in gastric cancer cell lines. Finally, blocking the lectin‑like oxLDL‑1 (LOX‑1) receptor, a specific receptor for oxLDL, and the nuclear factor (NF)‑κB signaling pathway following oxLDL (50 µg/ml) treatment in HGC‑27 cells revealed that oxLDL could activate the NF‑κB signaling pathway mediated by LOX‑1, with subsequent upregulation of VEGF‑C expression, and secretion in and from gastric cancer cells, and finally that it could promote the lymphatic metastasis of gastric cancer. These data indicate the association between the plasma oxLDL and the lymphatic metastasis of gastric cancer, and indicate that oxLDL elimination may be a potential therapeutic target for the prevention and intervention of early lymph node metastasis in gastric cancer.
胃癌是最恶性的肿瘤类型之一，其转移是导致死亡的重要原因。在肿瘤转移的方法中，淋巴转移是胃癌转移的主要方式。先前的研究表明，血浆氧化型低密度脂蛋白（oxLDL）是脂质代谢异常患者肿瘤发生的危险因素，但血浆 oxLDL 对胃癌淋巴转移的影响尚不清楚。本研究采用 ELISA 试剂盒检测胃癌患者血浆 oxLDL 浓度，采用 D2-40 染色检测胃癌组织中淋巴管密度。oxLDL 浓度与淋巴管密度的相关性分析表明，血浆 oxLDL 与胃癌患者的淋巴转移呈正相关。随后，裸鼠的鼠后淋巴结转移动物实验证实 oxLDL 可促进胃癌的淋巴转移。随后，Western blot 和 ELISA 数据表明，oxLDL 可促进胃癌细胞系中血管内皮生长因子（VEGF）-C 的表达和分泌。最后，阻断 oxLDL（50µg/ml）处理后 HGC-27 细胞中的凝集素样 oxLDL-1（LOX-1）受体和核因子（NF）-κB 信号通路表明，oxLDL 可激活 LOX-1 介导的 NF-κB 信号通路，随后上调 VEGF-C 的表达和分泌，并最终促进胃癌的淋巴转移。这些数据表明血浆 oxLDL 与胃癌的淋巴转移之间存在关联，并表明消除 oxLDL 可能是预防和干预胃癌早期淋巴结转移的潜在治疗靶点。
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