文献类型：期刊文献

英文题名：Astragaloside IV inhibits progression of lung cancer by mediating immune function of Tregs and CTLs by interfering with IDO

作者：Zhang, Anle[1,2];Zheng, Yuanhong[1,2];Que, Zujun[1,2];Zhang, Lingling[1,2];Lin, Shengchao[1,2];Vanminh Le[1,2];Liu, Jianwen[1,2];Tian, Jianhui[3]

机构：[1]E China Univ Sci & Technol, Dept Mol & Cellular Pharmacol, Biomed Nanotechnol Ctr, State Key Lab Bioreactor Engn, Shanghai 200237, Peoples R China;[2]E China Univ Sci & Technol, Shanghai Key Lab New Drug Design, Sch Pharm, Shanghai 200237, Peoples R China;[3]Shanghai Univ Tradit Chinese Med, Longhua Hosp, Shanghai 200032, Peoples R China

年份：2014

卷号：140

期号：11

起止页码：1883

外文期刊名：JOURNAL OF CANCER RESEARCH AND CLINICAL ONCOLOGY

收录：;WOS:【SCI-EXPANDED(收录号:WOS:000343819500008)】；

基金：This work was supported by the National Natural Science Foundation of China (NSFC project number: 81173224), Shanghai Committee of Science and Technology (no. 13140902300), the Shanghai Committee of Science and Technology (grant 11DZ2260600), and the Fundamental Research Funds for the Central Universities.

语种：英文

外文关键词：IDO; AS-IV; Immunotherapy; Regulatory T cells; Cytotoxic T lymphocytes

摘要：Tumor cells have developed multiple mechanisms to escape immune recognition mediated by T cells. Indoleamine 2,3-dioxygenase (IDO), a tryptophan-catabolizing enzyme inducing immune tolerance, is involved in tumor escape from host immune systems in mice. Astragaloside IV (AS-IV), an extract from a commonly used Chinese medicinal plant Astragalus membranaceus, has been shown to be capable of restoring the impaired T-cell functions in cancer patients. The purpose of this study was to investigate the mechanisms underlying the anticancer properties of AS-IV. Here, we used IDO-overexpressed murine Lewis lung carcinoma cells to establish an orthotopic lung cancer model in C57BL/6 mice. Next, tumor growth was evaluated in several different treatment groups: control (saline), AS-IV, paclitaxel, and 1-methyl tryptophan (an inhibitor of IDO). We then analyzed the percentages of various immune cell subsets among the splenic lymphocytes of lung cancer mice by flow cytometry. The level of IDO was measured by real-time PCR and Western blot. We showed that the growth of tumor was suppressed by AS-IV treatment in vivo. AS-IV also could down-regulate regulatory T cells (Tregs) and up-regulate cytotoxic T lymphocytes (CTLs) in vivo and in vitro. Consistent with its ability to interfere with T-cell immunity, AS-IV blocked IDO induction both in vitro and in vivo. The results of these studies indicate that AS-IV has in vivo anticancer activity and can enhance the immune response by inhibiting the Tregs frequency and induce the activity of CTLs, which might be related to the inhibition of IDO expression.