Oroxylin A inhibits the generation of Tregs in non-small cell lung cancer.
Oroxylin A inhibits the generation of Tregs in non-small cell lung cancer.
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Oroxylin A 抑制非小细胞肺癌中 Tregs 的生成
DOI：
10.18632/oncotarget.17218
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发表时间：
2017-07-25
期刊：
影响因子：
--
通讯作者：
Zhang S
中科院分区：
文献类型：
--
作者：
Shen L;Zhang LL;Li H;Liu X;Yu XX;Hu P;Hui H;Guo QL;Zhang S
Oroxylin A（OA）是一种天然存在的单克隆抗体，从黄芪中分离得到，先前已报道其抑制几种癌细胞系的增殖。CD 4 + CD 25 + Foxp 3+调节性T细胞（Regulatory T cells，Tcells）在维持免疫自身耐受中起重要作用。甲状腺激素在癌症中也会增加，并参与抑制抗肿瘤免疫反应。本文探讨了OA对肺癌环境中T细胞的影响及其机制。结果表明，OA可逆转H460肺癌细胞共培养诱导的TcB的产生。此外，在体内，OA降低肿瘤形成率和衰减肿瘤浸润淋巴细胞中Foxp 3的表达。我们还发现，在共培养模型中，转化生长因子-β1（TGF-β1）中和抗体逆转了Treg数量和p-Smad 3 β p-p38 β p-JNK β p-ERK 1/2表达的增加。OA还能抑制H460细胞TGF-β1的分泌，下调NF-κB信号的激活。OA还通过直接抑制T细胞对TGF-β1的反应来抑制Treg活性。结论：OA通过NF-κB信号通路抑制肺癌细胞TGF-β 1分泌，抑制肺癌细胞对TGF-β 1的反应，从而抑制肺癌细胞内TcB的生成。
Oroxylin A (OA), a naturally occurring monoflavonoid isolated from Scutellariae radix, has previously been reported to inhibit the proliferation of several cancer cell lines. CD4+CD25+Foxp3+ regulatory T cells (Tregs) play an important role in maintenance of immunologic self-tolerance. Tregs also increase in cancer and take part in suppressing antitumor immune responses. Here, we explored how OA affected the Tregs in lung cancer environment and the involved underlying mechanism. It is found that OA reversed the generation of Tregs induced by H460 lung cancer cells co-culture. Furthermore, in vivo, OA reduced tumor formation rate and attenuated Foxp3 expression in tumor-infiltrating lymphocytes. We also found that transforming growth factor-β1 (TGF-β1) neutralizing antibody reversed the enhancement of Treg number and expression of p-Smad3ˎ p-p38ˎp-JNKˎp-ERK1/2 in the co-culture model. Moreover, OA reduced the secretion of TGF-β1 and down-regulated the activation of NF-κB signaling in H460 cells. OA also inhibited Treg activity by a direct inhibition of the T cells' response to TGF-β1. In conclusion, our study demonstrated that OA inhibits the generation of Tregs in lung cancer environment by inhibiting the T cells' response to TGF-β1 and decreasing the secretion of TGF-β1 in lung cancer cells via NF-κB signaling.
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DOI：
10.1084/jem.161.1.72
发表时间：
1985-01-01
期刊：
The Journal of experimental medicine
影响因子：
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作者：
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影响因子：
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DOI：
10.1084/jem.20100945
发表时间：
2011-04-11
期刊：
The Journal of experimental medicine
影响因子：
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