title: Astragaloside IV inhibits progression of lung cancer by mediating immune function of Tregs and CTLs by interfering with IDO.
abstract: OBJECTIVE
  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.
  
  
  METHODS
  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.
  
  
  RESULTS
  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.
  
  
  CONCLUSIONS
  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.
authors: Department of Molecular & Cellular Pharmacology, Biomedical Nanotechnology Center, State Key Laboratory of Bioreactor Engineering and Shanghai Key Laboratory of New Drug Design, School of Pharmacy, East China University of Science and Technology, Shanghai, 200237, People's Republic of China.
authors: Anle
authors: A
authors: Zhang
authors: Yuanhong
authors: Y
authors: Zheng
authors: Zujun
authors: Z
authors: Que
authors: Lingling
authors: L
authors: Zhang
authors: Shengchao
authors: S
authors: Lin
authors: Vanminh
authors: V
authors: Le
authors: Jianwen
authors: J
authors: Liu
authors: Jianhui
authors: J
authors: Tian
mesh_terms: D000818:Animals; D000970:Antineoplastic Agents / Q000494:pharmacology* / Q000627:therapeutic use; D018827:Carcinoma, Lewis Lung / Q000188:drug therapy / Q000201:enzymology / Q000276:immunology* / Q000473:pathology; D045744:Cell Line, Tumor; D018920:Coculture Techniques; D018450:Disease Progression; D004354:Drug Screening Assays, Antitumor; D005260:Female; D050503:Indoleamine-Pyrrole 2,3,-Dioxygenase / Q000037:antagonists & inhibitors / Q000378:metabolism*; D008810:Mice, Inbred C57BL; D009368:Neoplasm Transplantation; D017239:Paclitaxel / Q000494:pharmacology / Q000627:therapeutic use; D012503:Saponins / Q000494:pharmacology* / Q000627:therapeutic use; D013602:T-Lymphocytes, Cytotoxic / Q000187:drug effects* / Q000276:immunology; D050378:T-Lymphocytes, Regulatory / Q000187:drug effects* / Q000276:immunology; D014315:Triterpenes / Q000494:pharmacology* / Q000627:therapeutic use; D014364:Tryptophan / Q000031:analogs & derivatives / Q000494:pharmacology / Q000627:therapeutic use; D047368:Tumor Burden / Q000187:drug effects; D019139:Tumor Escape / Q000187:drug effects
chemical_list: D000970:Antineoplastic Agents; C583637:IDO1 protein, mouse; D050503:Indoleamine-Pyrrole 2,3,-Dioxygenase; D012503:Saponins; D014315:Triterpenes; C052064:astragaloside A; D014364:Tryptophan; D017239:Paclitaxel; C525396:1-methyltryptophan