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

  • Original Article – Cancer Research
  • Published:
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Abstract

Purpose

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.

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Abbreviations

IDO:

Indoleamine 2,3-dioxygenase

AS-IV:

Astragaloside IV

Treg:

T regulatory cell

CTL:

Cytotoxic T lymphocyte

3LL:

Lewis lung carcinoma

1-MT:

1-Methyl tryptophan

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Acknowledgments

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.

Conflict of interest

The authors declare that they have no conflict of interest.

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Authors and Affiliations

  1. 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

    Anle Zhang, Yuanhong Zheng, Zujun Que, Lingling Zhang, Shengchao Lin, Vanminh Le & Jianwen Liu

  2. Longhua Hospital Affiliated to Shanghai University of Traditional Chinese Medicine, Shanghai, 200032, People’s Republic of China

    Jianhui Tian

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  1. Anle Zhang
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  2. Yuanhong Zheng
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  3. Zujun Que
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  4. Lingling Zhang
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  5. Shengchao Lin
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  7. Jianwen Liu
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Correspondence to Jianwen Liu or Jianhui Tian.

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Zhang, A., Zheng, Y., Que, Z. et al. Astragaloside IV inhibits progression of lung cancer by mediating immune function of Tregs and CTLs by interfering with IDO. J Cancer Res Clin Oncol 140, 1883–1890 (2014). https://doi.org/10.1007/s00432-014-1744-x

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  • DOI: https://doi.org/10.1007/s00432-014-1744-x

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