Toxicarioside A inhibits SGC-7901 proliferation, migration and invasion via NF-κB/bFGF signaling
Toxicarioside A inhibits SGC-7901 proliferation, migration and invasion via NF-κB/bFGF signaling
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DOI：
10.3748/wjg.v18.i14.1602
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发表时间：
2012-04-14
影响因子：
4.3
通讯作者：
Dai, Hao-Fu
中科院分区：
文献类型：
--
作者：
Guo, Jun-Li;Zheng, Shao-Jiang;Dai, Hao-Fu
目的：探讨毒胡萝卜甙A对胃癌细胞株人胃癌细胞株的抑制作用（SGC-7901）并确定潜在的分子机制。用不同浓度的毒胡萝卜甙A处理SGC-7901细胞，（0.5、1.5、4.5、9.0 μ g/mL）作用24小时或48小时后，通过3-（4，5-二甲基-噻唑-2-基）-2，5-二苯基-2H-溴化四唑测定法测定细胞活力，并通过Transwell小室测定法评估肿瘤细胞的运动性和侵袭性。采用免疫荧光染色、逆转录聚合酶链反应和蛋白质印迹法检测碱性成纤维细胞生长因子（bFGF）、成纤维细胞生长因子受体1（FGFR 1）和核因子-κ B（NF-κ B）的表达通过电泳迁移率变动分析检测（NF-κ B）活化。结果表明，毒胡萝卜甙A能降低SGC-7901细胞的存活率，抑制细胞生长，抑制细胞的迁移和侵袭能力，并呈时间和剂量依赖性。进一步分析发现，与对照组相比，毒胡萝卜甙A不仅能有效地抑制bFGF及其高亲和力受体FGFR 1的表达，而且能有效地抑制NF-κ B-DNA结合活性（P < 0.05或P < 0.01）。有趣的是，与对照组相比，NF-κ B特异性抑制剂吡咯烷二硫代氨基甲酸酯（PDTC）对SGC-7901细胞的应用显著增强了毒胡萝卜苷A诱导的bFGF下调（P < 0.05）。结论：这些结果表明，毒胡萝卜苷A具有抗胃癌活性，这种作用可能部分通过下调NF-κ B和bFGF/NF-κ B的表达来实现。FGFR 1信号传导。(C)2012年百世登。All rights reserved.
AIM: To investigate the inhibitory role of toxicarioside A on the gastric cancer cell line human gastric cancer cell line (SGC-7901) and determine the underlying molecular mechanism.METHODS: After SGC-7901 cells were treated with toxicarioside A at various concentrations (0.5, 1.5, 4.5, 9.0 mu g/mL) for 24 h or 48 h, cell viability was determined by 3-(4,5-dimethyl-thiazol-2-yl)-2,5-diphenyl-2H-tetrazolium bromide assay, and the motility and invasion of tumor cells were assessed by the Transwell chamber assay. Immunofluorescence staining, reverse transcription polymerase chain reaction and Western blotting were performed to detect the expression of basic fibroblast growth factor (bFGF) and fibroblast growth factor receptor-1 (FGFR1), and nuclear factor-kappa B (NF-kappa B) activation was examined by electrophoretic mobility shift assay.RESULTS: The results showed that toxicarioside A was capable of reducing cell viability, inhibiting cell growth, and suppressing cell migration and invasion activities in a time- and dose-dependent manner in SGC-7901 cells. Further analysis revealed that not only the expression of bFGF and its high-affinity receptor FGFR1 but also the NF-kappa B-DNA binding activity were effectively blocked by toxicarioside A in a dose-dependent manner compared with the control group (P < 0.05 or P < 0.01). Interestingly, application of the NF-kappa B specific inhibitor, pyrrolidinedithiocarbamate (PDTC), to SGC-7901 cells significantly potentized the toxicarioside A-induced down-regulation of bFGF compared with the control group (P < 0.05).CONCLUSION: These findings suggest that toxicarioside A has an anti-gastric cancer activity and this effect may be achieved partly through down-regulation of NF-kappa B and bFGF/FGFR1 signaling. (C) 2012 Baishideng. All rights reserved.