Tetrandrine inhibits migration and invasion of human renal cell carcinoma by regulating Akt/NF-κB/MMP-9 signaling.
Tetrandrine inhibits migration and invasion of human renal cell carcinoma by regulating Akt/NF-κB/MMP-9 signaling.
复制标题
粉防己碱通过调节 Akt/NF-kappa B/MMP-9 信号传导抑制人肾细胞癌的迁移和侵袭
DOI：
10.1371/journal.pone.0173725
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发表时间：
2017
期刊：
影响因子：
3.7
通讯作者：
Li L
中科院分区：
文献类型：
--
作者：
Chen S;Liu W;Wang K;Fan Y;Chen J;Ma J;Wang X;He D;Zeng J;Li L
肾细胞癌（RCC）被称为泌尿外科系统中最致命的恶性肿瘤之一，因为它的转移发生率很高。一种传统的中草药四兰（Tetrine）（TET）在多种癌细胞中发挥了有效的抗癌作用。但是，TET的抗转移效应及其在RCC中的可能机制尚不清楚。本研究表明，TET在体外显着抑制了RCC 786-O和769-P细胞的迁移和侵袭。从机械上讲，TET处理后，基质金属蛋白酶9（MMP-9），磷酸化的PI3K，PDK1，AKT和NF-κB的蛋白水平显着降低。此外，与LY294002（PI3K抑制剂）共同治疗可以进一步增强TET抑制的迁移和侵袭，而NF-κB和MMP-9蛋白水平进一步降低。 PDTC（NF-κB抑制剂）共同处理后观察到了相似的结果。相反，AKT激活剂SC79可以部分扭转TET的抗转移作用，并伴随着NF-κB和MMP-9蛋白水平的恢复。总之，目前的结果表明，TET通过调节AKT/NF-κB/MMP-9信号通路来部分抑制RCC的迁移和侵袭，这表明TET可能是针对转移性RCC的潜在治疗候选者。
Renal cell carcinoma (RCC) is known as one of the most lethal malignancies in the urological system because of its high incidence of metastasis. Tetrandrine (Tet), a traditional Chinese herbal medicine, exerts a potent anti-cancer effect in a variety of cancer cells. However, the anti-metastatic effect of Tet and its possible mechanism in RCC is still unclear. The present study revealed that Tet significantly suppressed the migration and invasion of RCC 786-O and 769-P cells in vitro. Mechanistically, the protein levels of matrix metalloproteinases 9 (MMP-9), phosphorylated PI3K, PDK1, Akt and NF-κB were markedly reduced after Tet treatment. Moreover, co-treatment with LY294002 (PI3K inhibitor) could further enhance the Tet-inhibited migration and invasion, and the NF-κB and MMP-9 protein levels were further decreased. Similar results were observed after PDTC (NF-κB inhibitor) co-treatment. Conversely, SC79, an Akt activator, could partially reverse the anti-metastatic effects of Tet, accompanied by the restoration of NF-κB and MMP-9 protein levels. In conclusion, the current results indicated that Tet inhibited migration and invasion of RCC partially by regulating Akt/NF-κB/MMP-9 signaling pathway, suggesting that Tet may be a potential therapeutic candidate against metastatic RCC.