Wogonin, an active ingredient of Chinese herb medicine Scutellaria baicalensis, inhibits the mobility and invasion of human gallbladder carcinoma GBC-SD cells by inducing the expression of maspin
Wogonin, an active ingredient of Chinese herb medicine Scutellaria baicalensis, inhibits the mobility and invasion of human gallbladder carcinoma GBC-SD cells by inducing the expression of maspin
复制标题
中药黄芩有效成分汉黄芩素通过诱导maspin表达抑制人胆囊癌GBC-SD细胞的迁移和侵袭
DOI：
10.1016/j.jep.2011.08.005
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发表时间：
2011-10-11
影响因子：
5.4
通讯作者：
Liu, Yingbin
中科院分区：
文献类型：
--
作者：
Dong, Ping;Zhang, Yong;Liu, Yingbin
民族药理学相关性：中药黄芩在我国临床上用于治疗多种炎症性疾病和肿瘤。本研究旨在探讨汉黄芩素对人胆囊癌GBC-SD细胞迁移和侵袭能力的影响及其作用机制。材料与方法：采用MTT法、Annexin V染色、实时荧光定量PCR和Western blot检测肿瘤细胞的存活率、凋亡率、mRNA和蛋白表达。迁移侵袭实验观察汉黄芩素的抗肿瘤转移作用。结果：汉黄芩素在1-10 μ M剂量下，对人胆囊癌GBC-SD细胞的迁移和侵袭能力有明显的抑制作用，但不诱导细胞凋亡。此外，基质金属蛋白酶（MMP）-2。MMP-9和磷酸化的细胞外调节蛋白激酶1/2（ERK 1/2），但不磷酸化Akt显着抑制汉黄芩素以浓度依赖性的方式。此外，转移抑制蛋白maspin被证实为汉黄芩素的下游靶点。汉黄芩素可上调maspin的mRNA和蛋白表达。有趣的是，敲低maspin导致几乎完全阻断汉黄芩素诱导的MMP-2，MMP-9和磷酸化ERK 1/2的抑制以及GBC-SD细胞的迁移和侵袭活性。结论：这些研究结果表明，汉黄芩素抑制细胞迁移和侵袭通过上调转移抑制maspin。总之，这些数据为汉黄芩素的化学保护作用提供了新的见解，汉黄芩素是中药黄芩的主要活性成分。(C)2011爱思唯尔爱尔兰有限公司保留所有权利。
Ethnopharmacological relevance: A traditional Chinese medicine Scutellaria baicalensis is prescribed for the treatment of a variety of inflammatory diseases and tumors in clinic in China. However, the detailed mechanism of anti-metastasis effect of wogonin, a main active ingredient of Scutellaria baicalensis, remains elusive.Aim of the study: The present study was designed to investigate the action and mechanism of wogonin on the mobility and invasion of human gallbladder carcinoma GBC-SD cells.Materials and methods: Viability, apoptosis, mRNA and protein expression of tumor cells were analyzed by MTT, Annexin V staining, real-time PCR and Western blot, respectively. The migration and invasion assay was used to evaluate the anti-metastasis effect of wogonin. Knockdown of maspin was performed by specific small interference RNA.Results: Wogonin at the dose of 1-10 mu M, which did not induce apoptosis, significantly inhibited the mobility and invasion activity of human gallbladder carcinoma GBC-SD cells. In addition, the expressions of matrix metalloproteinase (MMP)-2. MMP-9 and phosphorylated extracellular regulated protein kinase 1/2 (ERK1/2) but not phosphorylated Akt were dramatically suppressed by wogonin in a concentration-dependent manner. Furthermore, the metastasis suppressor maspin was confirmed as the downstream target of wogonin. Both maspin mRNA and protein were upregulated by wogonin. Interestingly, the knockdown of maspin resulted in almost completely blocking of wogonin-induced inhibition of MMP-2, MMP-9 and phosphorylated ERK1/2 as well as the mobility and invasion activity of GBC-SD cells.Conclusions: These findings suggest that wogonin inhibits cell mobility and invasion by upregulating the metastasis suppressor maspin. Together, these data provide novel insights into the chemoprotective effect of wogonin, a main active ingredient of Chinese medicine Scutellaria baicalensis. (C) 2011 Elsevier Ireland Ltd. All rights reserved.