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

Bin Luo; Zu-jun Que; Zhi-yi Zhou; Qing Wang; Chang-sheng Dong; Yi Jiang; Bing HU; Hui Shi; Yu Jin; Jian-wen Liu; He-gen LI; Lin Wang; Jian-hui Tian

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

Author: Bin LUO ¹ ; Zu-Jun QUE ² ; Zhi-Yi ZHOU ¹ ; Qing WANG ² ; Chang-Sheng DONG ² ; Yi JIANG ¹ ; Bing HU ^{3
,

4} ; Hui SHI ⁵ ; Yu JIN ⁵ ; Jian-Wen LIU ⁵ ; He-Gen LI ¹ ; Lin WANG ⁶ ; Jian-Hui TIAN ^{3
,

7}
Author Information

1. Department of Oncology, Longhua Hospital Affiliated to Shanghai University of Traditional Chinese Medicine, Shanghai 200032, China.
2. Oncology Institute of Traditional Chinese Medicine, Institute of TCM Oncology, Shanghai 200032, China.
3. Department of Oncology, Longhua Hospital Affiliated to Shanghai University of Traditional Chinese Medicine, Shanghai 200032, China
4. Oncology Institute of Traditional Chinese Medicine, Institute of TCM Oncology, Shanghai 200032, China.
5. School of Pharmacy, East China University of Science and Technology, Shanghai 200237, China.
6. Department of Nephrology, Longhua Hospital Affiliated to Shanghai University of Traditional Chinese Medicine, Shanghai 200032, China. Electronic address: happytlynn@163.com.
7. Oncology Institute of Traditional Chinese Medicine, Institute of TCM Oncology, Shanghai 200032, China. Electronic address: hawk7150@hotmail.com.
Publication Type:Journal Article
Keywords: Feiji Recipe; Immune escape; Indoleamine-2,3-dioxygenase; Orthotopic xenografts
MeSH: Animals; Apoptosis; drug effects; Carcinoma, Lewis Lung; drug therapy; enzymology; immunology; physiopathology; Cell Proliferation; drug effects; Disease Models, Animal; Drugs, Chinese Herbal; administration & dosage; Growth Inhibitors; administration & dosage; Humans; Indoleamine-Pyrrole 2,3,-Dioxygenase; genetics; immunology; Lung Neoplasms; drug therapy; enzymology; immunology; physiopathology; Male; Mice; Mice, Inbred C57BL; T-Lymphocytes, Regulatory; drug effects; immunology
From: Journal of Integrative Medicine 2018;16(4):283-289
CountryChina
Language:English
Abstract:
OBJECTIVEEscape 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.
METHODSAn 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.
RESULTSCompared 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 CD4CD25 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.
CONCLUSIONThe 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.