姜黄素抑制胃癌淋巴管生成相关因子的机制研究

Mechanism of anti-lymphangiogenesis related factors by curcumin in gastric cancer

[目的]本研究探讨姜黄素抑制淋巴管生成相关因子的可能分子机制。[方法] MTT检测MGC803细胞增殖情况,实时定量聚合酶链式反应(qRT-PCR)和蛋白质免疫印迹(Werstern Blot)检测细胞株中SMYD3(SET and MYND domain-containing protein 3)、VEGF(vascular endothelial growh factors)-C和VEGF-D mRNA和蛋白的表达。[结果]胃癌MGC803细胞株中加入SMYD3抑制剂BCI-121后,淋巴管生成因子VEGF-C和VEGF-D m RNA和蛋白表达明显降低;在稳定低表达SMYD3的细胞株(MGC803-sh-SMYD3)中,发现较MGC80细胞株,MGC803-sh-SMYD3细胞株中VEGF-C和VEGF-D mRNA和蛋白明显降低。MTT检测不同时间节点不同浓度姜黄素作用MGC803细胞株细胞增殖的差异,发现50μmol/Lol/L姜黄素对胃癌细胞抑制作用最强;姜黄素能够降低MGC803细胞株VEGF-C和VEGF-D mRNA和蛋白表达。BCI-121联合姜黄素处理MGC803细胞株后,较单独姜黄素处理,MGC803细胞株中VEGF-D mRNA和蛋白的表达降低,而VEGF-C无明显变化;进一步姜黄素处理MGC803和MGC803-sh-SMYD3细胞株后,同样发现MGC803-sh-SMYD3中VEGF-D mRNA和蛋白的表达降低,而VEGF-C变化不显著。[结论]姜黄素可能通过抑制SMYD3通路进而抑制淋巴管生成相关因子VEGF-D。

[Objective] To investigate the molecular mechanism of anti-lymphangiogenesis related factors by curcumin in gastric cancer.[Methods] The MTT was used to test the mobility of MGC803 cell lines. The SMYD3(SET and MYND domain-containing protein 3),VEGF(vascular endothelial growh factors)-C and VEGF-D mRNA and protein expression level were detected by quantitative real-time reverse transcription PCR and Werstern Blot. [Results] The expression of VEGF-C and VEGF-D mRNA and protein in MGC803 cell line were significantly lower after treating with SMYD3 inhibitor BCI-121 in MGC803 cell line. In low expression of SMYD3 cell line(MGC803-sh-SMYD3),the expression of VEGF-C and VEGF-D mRNA and protein were significantly lower than MGC803 cell line. MTT showed that 50 μmol/L curcumin had the strongest inhibitory effects,and the mRNA and protein expression levels of VEGF-C and VEGF-D were significantly eliminated by curcumin. Compared with treatment with curcumin alone,the expression of VEGF-D m RNA and protein were significantly decreased in MGC803 with treating both BCI-121 and curcumin. Furthermore,we found the expression of VEGF-D mRNA and protein in MGC803-sh-SMYD3 were decreased compared with MGC803 cell line when treated with curcumin,while not VEGF-C expression. [Conclusion] It suggested that curcumin might exert anti-VEGF-D in gastric cancer by inhibition of SMYD3 signaling.