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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

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Journal of Integrative Medicine 2018年第4期16卷 283-289页

作者： 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 Department of Oncology Longhua Hospital Affiliated to Shanghai University of Traditional Chinese Medicine Oncology Institute of Traditional Chinese Medicine Institute of TCM Oncology School of Pharmacy East China University of Science and Technology Department of Nephrology Longhua Hospital Affiliated to Shanghai University of Traditional Chinese Medicine

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.

关键词： Feiji Recipe Immune escape Orthotopic xenografts indoleamine-2,3-dioxygenase

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indoleamine-2,3-dioxygenase 1/cyclooxygenase 2 expression prediction for adverse prognosis in colorectal cancer

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World Journal of Gastroenterology 2018年第20期24卷 2181-2190页

作者： Wen-Juan Ma Xing Wang Wen-Ting Yan Zhong-Guo Zhou Zhi-Zhong Pan Gong Chen Rong-Xin Zhang State Key Laboratory of Oncology in South China Sun Yat-sen UniversityGuangzhou 510060Guangdong ProvinceChina Collaborative Innovation Center of Cancer Medicine Guangzhou 510060Guangdong ProvinceChina Tongji Medical College Huazhong University of Science and TechnologyWuhan 430074Hubei ProvinceChina Department of Hepatobiliary Surgery Cancer CenterSun Yat-sen UniversityGuangzhou 510060Guangdong ProvinceChina Department of Colorectal Surgery Cancer CenterSun Yat-sen UniversityGuangzhou 510060Guangdong ProvinceChina

AIM To evaluate indoleamine-2,3-dioxygenase 1/cyclooxygenase 2(IDO1/COX2) expression as an independent prognostic biomarker for colorectal cancer(CRC) *** We retrospectively studied the medical records of 95 patients who received surgical resection from August 2008 to January 2010. All patients were randomly assigned to adjuvant treatment with or without celecoxib groups after surgery. We performed standard immunohistochemistry to assess the expression levels of IDO1/COX2 and evaluated the correlation of IDO1/COX2 with clinicopathological factors and overall survival(OS) *** The expression of nuclear IDO1 was significantly correlated with body mass index(P 3+ and CD8+ tumor infiltrating lymphocytes, and COX2. In univariate analysis, we found that nuclear IDO1(P = 0.039), nuclear/cytoplasmic IDO1 [hazard ratio(HR) = 2.044, 95% confidence interval(CI): 0.871-4.798, P = 0.039], nuclear IDO1/COX2(HR = 3.048, 95%CI: 0.868-10.7, P = 0.0049) and cytoplasmic IDO1/COX2(HR = 2.109, 95%CI: 0.976-4.558, P = 0.022) all yielded significantly poor OS outcomes. Nuclear IDO1(P = 0.041), nuclear/cytoplasmic IDO1(HR = 3.023, 95%CI: 0.585-15.61, P = 0.041) and cytoplasmic IDO1/COX2(HR = 2.740, 95%CI: 0.764-9.831, P = 0.038) have significantly poor OS outcomes for the CRC celecoxib subgroup. In our multivariate Cox model, high coexpression of cytoplasmic IDO1/COX2 was found to be an independent predictor of poor outcome in CRC(HR = 2.218, 95%CI: 1.011-4.48, P = 0.047) and celecoxib subgroup patients(HR = 3.210, 95%CI: 1.074-9.590, P = 0.037).CONCLUSION Our results showed that cytoplasmic IDO1/COX2 coexpression could be used as an independent poor predictor for OS in CRC.

关键词： Prognosis indoleamine-2,3-dioxygenase 1 Cyclooxygenase 2 Colorectal cancer

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Recombinant adenovirus with human indoleamine-2,3- dioxygenase and hepatitis B virus preS was constructed and expressed in HepG2 cells

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Chinese Medical Journal 2011年第19期000卷 3159-3163页

作者： CHEN Yong-bing SHI Xian-jie LU Gang NIE Hong-feng SHEN Xiao-qing YU Cong-hui GONG Jian-ping Department of Hepatobilliary Surgery Beijng Military Region General Hospital Beijing 100700 China Department of Burn Surgery Beijng Military Region General Hospital Beijing 100700 China Department of Hepatobilliary Surgery General Hospital of People＇s Liberation Army Beijing 100853 China Department of Hepatobiliary Surgery Second Hospital Affiliated to Chongqing University of Medical Sciences Chongqing 400010 China

Background indoleamine-2,3-dioxygenase （IDO） is proven to suppress hepatitis B virus （HBV） specific immune response and depletion of IDO may be a useful approach for HBV therapy. To test this concept, we constructed recombinant adenovirus with human IDO and HBV preS, which would form the basis for future in vivo *** The fragment of human IDO and HBV preS cDNA were subcloned into multiple cloning sites in an adenoviral vector system containing two cytomegalovirus （CMV） promoters. Recombination was conducted in the Escherichia coli BJ5183. The recombinant adenovirus containing hlDO gene and HBVpreS gene was packaged and amplified in 293 *** was confirmed by polymerase chain reaction as well as the quantification of viral titers. HepG2 cells were infected with the recombinant adenovirus and mRNA and protein specific for hlDO and HBVpreS was detected by RT-PCR and Western blotting *** The recombinant adenovirus was produced successfully. Its titer was 2.5x109 efu/ml. IDO and HBVpreS mRNA as well as the encoded proteins could be found in transfected HepG2 cells, but not in control HepG2 *** The transfer of hlDO-HBVpreS with double-promoter adenoviral vector was efficient. The recombinant adenovirus with hlDO and HBVpreS would provide the experimental basis for future studies.

关键词： indoleamine-2,3-dioxygenase recombined adenovirus hepatitis B virus HepG2 cell

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