Accumulating evidence shows that curcumin exerts antitumor activities in a variety of malignancies. High mobility group box 1 (HMGB1) is associated with vascular endothelial growth factor D (VEGF-D)-induced lymphangiogenesis and tumor metastasis in gastric cancer. However, the molecular mechanisms by which curcumin regulates HMGB1-mediated lymphangiogenesis in gastric cancer remain unclear. In this study, the cytotoxic effects of curcumin were investigated in gastric cancer AGS and SGC-7901 cell lines by MTT assay, and curcumin-induced morphological changes and cell apoptosis were assessed by using flow cytometry analysis and caspase-3 activity. The effects of curcumin on HMGB1 and VEGF-D expression were examined by reverse transcription polymerase chain reaction (RT-PCR) and western blot analysis. As a result, we found that curcumin decreased cell viability and caused a dose-dependent cell apoptosis through the activation of caspase-3. The mRNA and protein expression levels of HMGB1 and VEGF-D were significantly eliminated by curcumin administration. Pre-treatment with the recombinant HMGB1 (rHMGB1) markedly abolished curcumin-reduced VEGF-D expression. Our findings suggested that curcumin might exert anti-lymphangiogenesis in gastric cancer by inhibition of HMGB1/VEGF-D signaling.

中文翻译：

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姜黄素通过抑制HMGB1 / VEGF-D信号传导来抑制胃癌细胞的淋巴管生成。

越来越多的证据表明姜黄素可在多种恶性肿瘤中发挥抗肿瘤活性。高迁移率族盒1（HMGB1）与血管内皮生长因子D（VEGF-D）诱导的胃癌淋巴管生成和肿瘤转移有关。然而，姜黄素调节胃癌中HMGB1介导的淋巴管生成的分子机制仍不清楚。本研究通过MTT法研究姜黄素对胃癌AGS和SGC-7901细胞系的细胞毒作用，并通过流式细胞术和caspase-3活性评估姜黄素诱导的形态变化和细胞凋亡。通过逆转录聚合酶链反应（RT-PCR）和western印迹分析检查姜黄素对HMGB1和VEGF-D表达的影响。结果是，我们发现姜黄素会降低细胞活力，并通过激活caspase-3引起剂量依赖性细胞凋亡。姜黄素给药可显着消除HMGB1和VEGF-D的mRNA和蛋白表达水平。重组HMGB1（rHMGB1）的预处理显着消除了姜黄素降低的VEGF-D表达。我们的发现表明姜黄素可能通过抑制HMGB1 / VEGF-D信号传导而在胃癌中发挥抗淋巴管生成的作用。