Department of Oncology, Longhua Hospital Affiliated to Shanghai University of Traditional Chinese Medicine, Shanghai 200032, China.
Oncology Institute of Traditional Chinese Medicine, Institute of TCM Oncology, Shanghai 200032, China.
J Integr Med. 2018 Jul;16(4):283-289. doi: 10.1016/j.joim.2018.04.008. Epub 2018 Apr 22.
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.
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.
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 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.
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.
逃避免疫系统的识别是肺癌的基本特征，色氨酸 2,3-双加氧酶（IDO）在介导非小细胞肺癌的免疫逃逸中起关键作用，导致复发和转移。肺积方是一种复方中药，具有稳定病灶和延长肺癌患者生存时间的作用。本研究旨在探讨肺积方的抗癌作用机制。
建立 C57BL/6 小鼠稳定表达 IDO 基因的原位移植模型，采用光学成像观察肺积方对荷瘤小鼠体内肺癌的治疗作用。观察肺积方对小鼠Lewis 肺癌细胞系 2LL、2LL-增强型绿色荧光蛋白（2LL-EGFP）和 2LL-EGFP-IDO 增殖的影响，采用 3-(4,5-二甲基-2-噻唑基)-2,5-二苯基-2H-四唑溴盐（MTT）比色法检测 T 细胞的凋亡情况。采用高效液相色谱法验证肺积方的化学成分。
与对照组相比，肺积方治疗组动物的生存时间明显延长（P=0.0074），IDO 蛋白水平降低（P=0.0072）；此外，CD4+CD25+T 细胞和 Foxp3+T 细胞的比例明显降低（P<0.05）。肺积方治疗肺癌的分子机制可能与调节 T 细胞和调节性 T 细胞等免疫细胞有关。
肺积方治疗肺癌的分子机制可能是通过干扰 IDO 通路，恢复肿瘤微环境中 T 细胞的功能。
