目的研究肺积方对吲哚胺-2,3-双加氧酶(indoleamine 2,3-dioxygenase,IDO)诱导Lewis肺癌(Lewis lung carcinoma,LL/2)小鼠模型免疫逃逸的影响。方法采用C57BL/6小鼠建立LL/2-增强型绿色荧光蛋白(enhanced green fluorescent protein,EGF...目的研究肺积方对吲哚胺-2,3-双加氧酶(indoleamine 2,3-dioxygenase,IDO)诱导Lewis肺癌(Lewis lung carcinoma,LL/2)小鼠模型免疫逃逸的影响。方法采用C57BL/6小鼠建立LL/2-增强型绿色荧光蛋白(enhanced green fluorescent protein,EGFP)-IDO模型48只,将小鼠按随机数字表分为模型组(灌胃生理盐水)、中药组[灌胃肺积方水煎液100mg/(g·d)]、1-甲基-D-色氨酸(1-methyl-D-tryptophan,1-MT)治疗组[灌胃1-MT混合液100mg/(kg·d)]和紫杉醇组[腹腔注射紫杉醇15mg/(kg·d)],每组12只。造模后第2日开始干预,其中24只观察小鼠生存期,余24只在造模并干预28日后采用流式细胞术检测脾脏CD4^+CD25^+FoxP3^+调节性T细胞(regulatory T cells,Treg)比例。结果与模型组比较,中药组、1-MT组生存期延长(P<0.01),中药组、1-MT组、紫杉醇组Treg比例降低(P<0.01)。与紫杉醇组比较,中药组、1-MT组生存期延长(P<0.01),1-MT组Treg比例降低(P<0.05)。结论肺积方能抑制肺癌细胞的增殖,抑制免疫逃逸,改善免疫功能,延长荷瘤小鼠生存期。展开更多
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 le...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 investi- gated, and the apoptosis of T-cells was examined by 3-（4,5-dimethyl-2-thiazolyl）-2,5-diphenyl-2H-tetra zolium 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 reg- ulatory 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.展开更多
Lung cancer is the leading cause of cancer-related mortality in the world. Although surgery, chemotherapy and radiotherapy can improve the survival rate l, cancers still affect people's quality of life. Feiji Reci...Lung cancer is the leading cause of cancer-related mortality in the world. Although surgery, chemotherapy and radiotherapy can improve the survival rate l, cancers still affect people's quality of life. Feiji Recipe is an empirical formula and has been used as a treatment for non-small cell lung cancer(NSCLC) for many years. This thesis collects data of the etiology and pathogenesis of Feiji Recipe, clinical research and animal experiments,and provide suggestive evidence of Feiji Recipe for treating NSCLC. During the treatment, the characteristic of holism and personalized treatment of traditional Chinese medicine(TCM)is proved, which also demonstrated that it can relieve patient's clinical syndrome, improve their quality of life and enhance the body immunity. It plays an irreplaceable role in lung cancer treatment.展开更多
文摘目的研究肺积方对吲哚胺-2,3-双加氧酶(indoleamine 2,3-dioxygenase,IDO)诱导Lewis肺癌(Lewis lung carcinoma,LL/2)小鼠模型免疫逃逸的影响。方法采用C57BL/6小鼠建立LL/2-增强型绿色荧光蛋白(enhanced green fluorescent protein,EGFP)-IDO模型48只,将小鼠按随机数字表分为模型组(灌胃生理盐水)、中药组[灌胃肺积方水煎液100mg/(g·d)]、1-甲基-D-色氨酸(1-methyl-D-tryptophan,1-MT)治疗组[灌胃1-MT混合液100mg/(kg·d)]和紫杉醇组[腹腔注射紫杉醇15mg/(kg·d)],每组12只。造模后第2日开始干预,其中24只观察小鼠生存期,余24只在造模并干预28日后采用流式细胞术检测脾脏CD4^+CD25^+FoxP3^+调节性T细胞(regulatory T cells,Treg)比例。结果与模型组比较,中药组、1-MT组生存期延长(P<0.01),中药组、1-MT组、紫杉醇组Treg比例降低(P<0.01)。与紫杉醇组比较,中药组、1-MT组生存期延长(P<0.01),1-MT组Treg比例降低(P<0.05)。结论肺积方能抑制肺癌细胞的增殖,抑制免疫逃逸,改善免疫功能,延长荷瘤小鼠生存期。
基金supported by National Natural Science Foundation of China(No.81173224 and 81373621)Shanghai Municipal Committee of Science and Technology(No.11ZR1437000)+3 种基金the Science and Technology Commission of Shanghai Municipality(No.12401905700)Longhua Medical Project(D-11)(all to Jian-hui Tian)State Administration of Traditional Chinese Medicine Clinical Research Base Special Project(No.JDZX2012125)(He-gen Li)Action Plan of Shanghai Chinese Medicine for Three Years(No.ZY3-CCCX-2-1002)(Zhen Xiao)
文摘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 investi- gated, and the apoptosis of T-cells was examined by 3-（4,5-dimethyl-2-thiazolyl）-2,5-diphenyl-2H-tetra zolium 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 reg- ulatory 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.
文摘Lung cancer is the leading cause of cancer-related mortality in the world. Although surgery, chemotherapy and radiotherapy can improve the survival rate l, cancers still affect people's quality of life. Feiji Recipe is an empirical formula and has been used as a treatment for non-small cell lung cancer(NSCLC) for many years. This thesis collects data of the etiology and pathogenesis of Feiji Recipe, clinical research and animal experiments,and provide suggestive evidence of Feiji Recipe for treating NSCLC. During the treatment, the characteristic of holism and personalized treatment of traditional Chinese medicine(TCM)is proved, which also demonstrated that it can relieve patient's clinical syndrome, improve their quality of life and enhance the body immunity. It plays an irreplaceable role in lung cancer treatment.
