Feiji Recipe inhibits the growth of lung cancer by modulating T-cell immunity through indoleamine-2,3-dioxygenase pathway in an orthotopic implantation model

J Integr Med. 2018 Jul;16(4):283-289. doi: 10.1016/j.joim.2018.04.008. Epub 2018 Apr 22.

Abstract

Objective: Escape from the body's immune response is a basic characteristic of lung cancer, and indoleamine-2,3-dioxygenase (IDO) plays a key role in mediating immune escape of non-small-cell lung cancer, which leads to recurrence and metastasis. Feiji Recipe, a compound Chinese herbal medicine, has the effect of stabilizing lesions and prolonging survival in patients with lung cancer. The purpose of this study was to investigate the mechanisms underlying the anticancer properties of Feiji Recipe.

Methods: An orthotopic transplant model of mouse Lewis lung cancer, with stable expression of IDO gene, was established in C57BL/6 mice. Optical imaging was used to observe the effects of Feiji Recipe in the treatment of lung cancer in vivo. The effects of Feiji Recipe on the proliferation of mouse Lewis lung cancer cell line 2LL, 2LL-enhanced green fluorescent protein (2LL-EGFP) and 2LL-EGFP-IDO were investigated, and the apoptosis of T-cells was examined by 3-(4,5-dimethyl-2-thiazolyl)-2,5-diphenyl-2H-tetrazolium bromide using flow cytometry. Chemical composition of Feiji Recipe was validated by high-performance liquid chromatography.

Results: Compared to the control group, the survival of animals treated with Feiji Recipe was significantly prolonged (P = 0.0074), and the IDO protein level decreased (P = 0.0072); moreover, the percentages of CD4+CD25+ T-cells and Foxp3+ T-cells were significantly decreased (P < 0.05). The molecular mechanism of Feiji Recipe against lung cancer may relate to the regulation of immune cells, such as T-cells and regulatory T-cells.

Conclusion: The molecular mechanism of Feiji Recipe in treatment of lung cancer is to restore the function of T-cells in the cancer microenvironment through interfering with the IDO pathway.

Keywords: Feiji Recipe; Immune escape; Indoleamine-2,3-dioxygenase; Orthotopic xenografts.

MeSH terms

  • Animals
  • Apoptosis / drug effects
  • Carcinoma, Lewis Lung / drug therapy*
  • Carcinoma, Lewis Lung / enzymology
  • Carcinoma, Lewis Lung / immunology
  • Carcinoma, Lewis Lung / physiopathology
  • Cell Proliferation / drug effects*
  • Disease Models, Animal
  • Drugs, Chinese Herbal / administration & dosage*
  • Growth Inhibitors / administration & dosage*
  • Humans
  • Indoleamine-Pyrrole 2,3,-Dioxygenase / genetics
  • Indoleamine-Pyrrole 2,3,-Dioxygenase / immunology*
  • Lung Neoplasms / drug therapy*
  • Lung Neoplasms / enzymology
  • Lung Neoplasms / immunology
  • Lung Neoplasms / physiopathology
  • Male
  • Mice
  • Mice, Inbred C57BL
  • T-Lymphocytes, Regulatory / drug effects
  • T-Lymphocytes, Regulatory / immunology

Substances

  • Drugs, Chinese Herbal
  • Growth Inhibitors
  • Indoleamine-Pyrrole 2,3,-Dioxygenase
  • feiji