Wogonin Inhibits Tumor-derived Regulatory Molecules by Suppressing STAT3 Signaling to Promote Tumor Immunity
Wogonin Inhibits Tumor-derived Regulatory Molecules by Suppressing STAT3 Signaling to Promote Tumor Immunity
复制标题
汉黄芩素通过抑制 STAT3 信号传导来抑制肿瘤衍生的调节分子，从而促进肿瘤免疫
DOI：
10.1097/cji.0000000000000080
复制
发表时间：
2015-06
影响因子：
3.9
通讯作者：
Gong, Weijuan
中科院分区：
文献类型：
--
作者：
Lu, Guotao;Deng, Bing;Bo, Ping;Gong, Weijuan
枸杞素通过对癌细胞的直接细胞毒作用和间接免疫调节作用发挥有效的抗肿瘤活性。然而，这些活动的分子机制仍然知之甚少，需要进一步研究。我们发现，wogonin可以有效下调B7H1、维甲酸早期诱导的转录-1和egr的表达；（RAE-1&egr;）和血管内皮生长因子在胃癌细胞中的表达。Wogonin还能促进肿瘤细胞钙网蛋白和高迁移率组蛋白1的分泌。死亡肿瘤细胞的凋亡小体易被邻近的树突状细胞（dc）摄取。在异种移植肿瘤模型中，wogonin抑制肿瘤生长，促进DC、T和NK细胞向肿瘤组织募集。DC、T、NK细胞在肿瘤中的浸润频率与血管内皮生长因子、B7H1、RAE-1&egr的表达水平呈负相关；肿瘤组织。Wogonin直接抑制肿瘤细胞中酪氨酸705上STAT3的激活。STAT3的去磷酸化导致B7H1和MHC I类链相关蛋白A的表达降低，细胞膜上钙调蛋白的表达增强。我们的研究证实了沃戈宁的免疫增强功能，并提示沃戈宁可与DC疫苗或活化淋巴细胞协同用于肿瘤治疗。
Wogonin exerts effective antitumor activities through direct cytotoxicity against cancer cells and indirect immune modulation. However, the molecular mechanisms of these activities remain poorly understood and need further study. We found that wogonin could efficiently downregulate the expression of B7H1, retinoic acid early induced transcript-1&egr; (RAE-1&egr;), and vascular endothelial growth factor in gastric cancer cells. Wogonin also promoted the secretion of calreticulin and high-mobility group protein 1 by tumor cells. Apoptotic bodies from dying tumor cells treated with wogonin were susceptible for uptake by neighboring dendritic cells (DCs). With the xenograft tumor model, wogonin inhibited tumor growth and promoted the recruitment of DC, T, and NK cells into tumor tissues. Infiltrated frequencies of DC, T, and NK cells in tumors were inversely correlated with expression levels of vascular endothelial growth factor, B7H1, and RAE-1&egr; of tumor tissues. Wogonin directly inhibited the activation of STAT3 on tyrosine 705 in tumor cells. The dephosphorylation of STAT3 contributed to the decreased expression of B7H1 and MHC class I chain-related protein A, and the enhancement of calreticulin on the cell membrane. Our study confirmed the immune-enhancing function of wogonin, and indicated that wogonin could be used in collaboration with DC vaccine or activated lymphocytes for tumor therapy.
登录
查看更多内容
影响因子：
5.8
作者：
Dandawate, Sagar;Williams, Linford;Joshee, Nirmal;Rimando, Agnes M.;Mittal, Sandeep;Thakur, Archana;Lum, Lawrence G.;Parajuli, Prahlad
通讯作者：
Parajuli, Prahlad
汉黄芩素通过 ROS 介导的 cFLIPL 和 IAP 蛋白下调增强体内肿瘤坏死因子相关凋亡诱导配体的抗肿瘤活性
影响因子：
7.2
作者：
Yang, Lan;Wang, Xia;Wang, Qiong;Li, Daoxia;Zhou, Yuqiong;Zheng, Xuelian;Sun, Hong;Yan, Jiaqi;Zhang, Lin;Lin, Yong
通讯作者：
Lin, Yong
影响因子：
2
作者：
Wang, Wei;Guo, Qing-Long;Wang, Xiao-Tang
通讯作者：
Wang, Xiao-Tang
影响因子：
3.9
作者：
Parajuli P;Joshee N;Chinni SR;Rimando AM;Mittal S;Sethi S;Yadav AK
通讯作者：
Yadav AK
影响因子：
3.7
作者：
Chen XM;Bai Y;Zhong YJ;Xie XL;Long HW;Yang YY;Wu SG;Jia Q;Wang XH
通讯作者：
Wang XH