Da Wei, Zhu Jinshui, Wang Long, Sun Qun
Department of Gastroenterology, Sixth People's Hospital Affiliated to Shanghai Jiaotong University, 600 Yishan Road, 200233, Shanghai, China.
Tumour Biol. 2015 Jul;36(7):5215-23. doi: 10.1007/s13277-015-3178-8. Epub 2015 Feb 10.
This study aimed to assess the effects of curcumin on lymphatic vessel density (LVD) in an in vivo model of gastric cancer using the gastric cancer cell line, SGC-7901. Gastric tumor-bearing nude mice were treated with saline or 40, 80, or 160 mg kg(-1) day(-1) curcumin for 8 weeks. The results indicated that the tumor volumes were significantly lower in mice treated with 80 and 160 mg kg(-1) day(-1) curcumin as compared with that of the control group (both P < 0.001). In addition, both 80 and 160 mg kg(-1) day(-1) curcumin significantly reduced LVD (both P < 0.01). Although immunohistochemical analysis showed that curcumin did not significantly alter the expression of prospero homeobox 1 (Prox-1), podoplanin, and vascular endothelial growth factor receptor 3 (VEGFR-3), 160 mg kg(-1) day(-1) curcumin significantly decreased the expression of Prox-1, podoplanin, and VEGFR-3 levels as detected by Western blot analysis (P ≤ 0.03). Downregulation of lymphatic vessel endothelial receptor 1 (LYVE-1), Prox-1, podoplanin, and VEGFR-3 mRNA expression by curcumin was also detected (all P < 0.05). Furthermore, the apoptosis rates of tumor cells increased with curcumin in a concentration-dependent manner (all P < 0.001). Thus, curcumin may inhibit gastric cancer lymph node metastasis. Our findings provide theoretical evidence and an experimental basis for further analysis of the clinical application of curcumin in the therapy of gastric cancer.
本研究旨在利用胃癌细胞系SGC - 7901,在胃癌体内模型中评估姜黄素对淋巴管密度(LVD)的影响。将荷胃癌裸鼠用生理盐水或40、80或160 mg·kg⁻¹·d⁻¹的姜黄素处理8周。结果表明,与对照组相比,接受80和160 mg·kg⁻¹·d⁻¹姜黄素处理的小鼠肿瘤体积显著更小(均P < 0.001)。此外,80和160 mg·kg⁻¹·d⁻¹的姜黄素均显著降低了LVD(均P < 0.01)。虽然免疫组化分析显示姜黄素未显著改变prospero同源盒1(Prox - 1)、血小板内皮细胞黏附分子(podoplanin)和血管内皮生长因子受体3(VEGFR - 3)的表达,但通过蛋白质印迹分析检测发现,160 mg·kg⁻¹·d⁻¹的姜黄素显著降低了Prox - 1、podoplanin和VEGFR - 3的水平(P≤0.03)。还检测到姜黄素下调了淋巴管内皮受体1(LYVE - 1)、Prox - 1、podoplanin和VEGFR - 3的mRNA表达(均P < 0.05)。此外,肿瘤细胞的凋亡率随姜黄素浓度的增加而呈浓度依赖性升高(均P < 0.001)。因此,姜黄素可能抑制胃癌淋巴结转移。我们的研究结果为进一步分析姜黄素在胃癌治疗中的临床应用提供了理论依据和实验基础。