Wogonoside inhibits invasion and migration through suppressing TRAF2/4 expression in breast cancer.
Wogonoside inhibits invasion and migration through suppressing TRAF2/4 expression in breast cancer.
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汉黄芩苷通过抑制乳腺癌中 TRAF2/4 的表达来抑制侵袭和迁移
DOI：
10.1186/s13046-017-0574-5
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发表时间：
2017-08-03
期刊：
影响因子：
--
通讯作者：
Lu N
中科院分区：
文献类型：
--
作者：
Yao Y;Zhao K;Yu Z;Ren H;Zhao L;Li Z;Guo Q;Lu N
Twist 1参与肿瘤的发生和发展，尤其是参与肿瘤的侵袭和转移。汉黄芩苷是汉黄芩素的主要体内代谢产物，也是一种具有潜在抗癌作用的天然产物。本研究旨在探讨汉黄芩苷对乳腺癌细胞的体外抗侵袭和体内抗转移作用及其机制。结果表明，汉黄芩苷在MDA-MB-231细胞原位移植模型中能抑制乳腺癌的生长和转移。汉黄芩苷可降低肿瘤晚期TNF-α、TRAF 2和TRAF 4的过度表达，改善肿瘤微环境。因此，TNF-α在体外诱导乳腺癌细胞转移。汉黄芩苷可抑制TNF-α诱导的MDA-MB-231、MDA-MB-435和BT-474细胞的侵袭和迁移。汉黄芩苷通过降低TRAF 2/4的蛋白表达，进而抑制Twist 1的表达，抑制NF-κB信号通路。汉黄芩苷可下调TNF-α诱导的MDA-MB-231和MDA-MB-435细胞MMP-9、MMP-2、vimentin和CD 44 v6的表达。在TNF-α + TGF-β1诱导的MCF-7细胞中证实了上述结果。汉黄芩苷可能是一种潜在的治疗乳腺癌转移的药物。
Twist1 is involved in tumor initiation and progression, which especially contributes to tumor invasion and metastasis. Wogonoside is the main in-vivo metabolite of wogonin, and it is also a natural product with potential treatment effects against cancer. In this study, we investigated the in-vitro anti-invasion and in-vivo anti-metastasis effects of wogonoside on breast cancer cells and uncovered its underlying mechanism. The results showed that wogonoside could suppress the growth and metastasis of breast tumor in the orthotopic model of MDA-MB-231 cells. We found that wogonoside could reduce the overexpression of TNF-α, TRAF2 and TRAF4 in later stage of tumor, and improved tumor microenvironment. Therefore, TNF-α was utilized to induce metastases of breast cancer cell in vitro. Wogonoside could inhibit invasion and migration in TNF-α-induced MDA-MB-231, MDA-MB-435, and BT-474 cells. Mechanically, wogonoside inactivated NF-κB signaling through decreasing the protein expression of TRAF2/4, which further inhibited Twist1 expression. Consequently, wogonoside could down-regulate MMP-9, MMP-2, vimentin and CD44v6 expression in TNF-α-induced MDA-MB-231 and MDA-MB-435 cells. Then, these findings were proved in TNF-α + TGF-β1-induced MCF7 cells. Wogonoside might be a potential therapeutic agent for the treatment of tumor metastasis in breast cancer.
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影响因子：
50.3
作者：
Ansieau, Stephane;Bastid, Jeremy;Puisieux, Alain
通讯作者：
Puisieux, Alain
影响因子：
4.6
作者：
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通讯作者：
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影响因子：
11.2
作者：
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影响因子：
4.2
作者：
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通讯作者：
Sliva D
影响因子：
15.9
作者：
Huber, MA;Azoitei, N;Wirth, T
通讯作者：
Wirth, T