[an error occurred while processing this directive]

Journal of Chinese Integrative Medicine ›› 2012, Vol. 10 ›› Issue (5): 584-590.doi: 10.3736/jcim20120515

• Original Experimental Research • Previous Articles     Next Articles

Effects of Chinese herbal medicine Feiyanning Decoction on the ratio of CD4+CD25+ regulatory T cells and expression of transcription factor Foxp3 in mice bearing Lewis lung carcinoma

Jing Guo, Ju-yong Wang, Zhan Zheng, Qing Wang, Chang-sheng Dong#br#   

  1. Institute of Oncology of Traditional Chinese Medicine, Longhua Hospital, Shanghai University of Traditional Chinese Medicine, Shanghai 200032, China
  • Received:2011-09-06 Accepted:2011-11-23 Online:2012-05-20 Published:2018-06-15

RichHTML

2

PDF (PC)

72

Like

Objective: To study the effects of Feiyanning Decoction, a compound traditional Chinese herbal medicine, on the ratio of CD4 +CD25 + regulatory T cells and expression of transcription factor Foxp3 in mice with Lewis lung cancer.

Methods: Thirty-two male wild-type C57BL/6 mice aging from 6 to 8 weeks were inoculated with Lewis lung cancer cells to establish the tumor-bearing model of Lewis lung carcinoma and were randomly divided into model group, Chinese medicine group, chemotherapy group and Chinese medicine combined with chemotherapy group. After intervention for 14 d with corresponding drugs, behaviors, physical signs and changes of feed consumption of the mice were observed. All mice were sacrificed after drug treatment, and tumors and organs were removed to weigh and calculate organ indexes (lung index, spleen index and thymus index). The percentages of CD4 +CD25 + regulatory T cells in the thymus, spleen and tumor were determined by flow cytometry. The expression of Foxp3 mRNA in the thymus, spleen and tumor tissues was detected by quantitative real-time polymerase chain reaction.

Results: Compared with those in the model group, the mice in the Chinese medicine group showed significant reductions in spleen and thymus indexes and tumor weight, and elevation in the body weight without tumor (P<0.05). The numbers of CD4 +CD25 + regulatory T cells in spleen, thymus and tumor were lower in the Chinese medicine group than in the model group (P<0.05). The expression of Foxp3 mRNA in spleen, thymus and tumor was significantly down-regulated in the Chinese medicine group compared with the model group (P<0.05). There were no significant differences in CD4 +CD25 + regulatory T cell ratio and Foxp3 mRNA expression between the Chinese medicine combined with chemotherapy group and the chemotherapy group.

Conclusion: Feiyanning Decoction can enhance the antitumor immune response and thus play a role in antitumor therapy by reducing the ratio of CD4 +CD25 + regulatory T cells and down-regulating the expression of Foxp3 mRNA.

Key words: Lewis lung cancer, regulatory T cells, Foxp3, drugs, Chinese herbal, mice

Table 1

Primer sequences and the product lengths for PCR analysis"

Target gene Forward primer and reverse primer Fragment length (bp) Annealing temperature (℃) Cycle
Foxp3 F: 5′-TAGTTCCTTCCCAGAGTTCTTCC-3′ 382 65.0 40
R: 5′-AGATTTCATTGAGTGTCCTCTGC-3′
β-actin F: 5′-CACCCGCGAGTACAACCTTC-3′ 207 60.4 40
R: 5′-CCCATACCCACCATCACACC-3′

Table 2

Dynamic changes in daily consumption of food of mice"

Group n Consumption of food of each group (g)
Day 0 Day 3 Day 7 Day 11 Day 15
Model 8 18.66 18.40 23.94 21.17 20.37
Chinese medicine 8 18.07 18.45 23.03 22.99 22.94
Chemotherapy 8 18.57 18.19 13.50 11.15 8.22
Combined treatment 8 18.55 18.35 15.82 13.18 13.13

Table 3

Dynamic changes in body weight of mice (x±s)"

Group n Body weight (g)
Day 0 Day 3 Day 7 Day 11 Day 15
Model 8 18.62±0.65 19.09±0.66 19.99±0.71 20.42±0.77 20.45±0.70
Chinese medicine 8 18.55±0.80 19.12±0.90 19.74±0.83 20.23±0.82 20.71±0.80
Chemotherapy 8 18.42±0.54 18.01±0.49 16.81±0.38 15.99±0.33 15.39±0.50
Combined treatment 8 18.47±0.56 18.15±0.62 17.55±0.55△ 16.41±0.86 15.55±0.58

Table 4

Changes in body weight, body weight without tumor, tumor weight and inhibition rate of tumor of mice"

Group n Body weight
(x±s, g)		 Body weight without tumor
(x±s, g)		 Tumor weight
(x±s, g)		 Inhibition rate of tumor
(%)
Model 8 20.45±0.70 16.29±0.79 4.16±0.33 —
Chinese medicine 8 20.71±0.80 17.42±0.82** 3.29±0.19** 20.91
Chemotherapy 8 15.39±0.50 13.43±0.58 1.95±0.34 53.13
Combined treatment 8 15.55±0.58 14.05±0.64△△ 1.51±0.20 63.70

Table 5

Lung, spleen and thymus indexes of mice (x±s)"

Group n Index of organs (mg/g)
Lung Spleen Thymus
Model 8 11.01±1.26 9.54±0.75 4.76±0.4
Chinese medicine 8 10.59±1.31 8.22±0.64** 4.12±0.29*
Chemotherapy 8 12.40±1.13 5.63±0.78 2.95±0.32
Combined treatment 8 11.54±1.32 6.31±0.34△ 3.36±0.26△

Table 6

Ratio of CD4+CD25+ Treg cells in spleen, thymus and tumor tissue of mice (x±s)"

Group n Ratio of CD4+CD25+ Treg cells (%)
Spleen Thymus Tumor
Model 3 25.23±0.96 23.23±0.61 27.28±0.94
Chinese medicine 3 22.12±1.12* 20.46±1.29* 21.85±0.92**
Chemotherapy 3 20.45±1.05 20.35±1.05 20.88±0.90
Combined treatment 3 18.36±0.84 17.26±0.79 18.43±0.79

Table 7

Expression of Foxp3 mRNA in spleen, thymus and tumor tissue of mice (x±s)"

Group n Foxp3+ mRNA
Spleen Thymus Tumor
Model 3 1.40±0.09 1.37±0.05 1.43±0.04
Chinese medicine 3 1.13±0.05* 1.19±0.04* 1.25±0.08*
Chemotherapy 3 1.06±0.08 1.07±0.07 1.05±0.08
Combined treatment 3 1.03±0.08 1.02±0.09 1.02±0.08
[1] Jemal A, Bray F, Center MM, Ferlay J, Ward E, Forman D . Global cancer statistics. CA Cancer[J] Clin. 2011; 61(2):69-90.
[2] Mackinnon AC, Kopatz J, Sethi T . The molecular and cellular biology of lung cancer: identifying novel therapeutic strategies[J].Br Med Bull, 2010, 95: 47-61.
doi: 10.1093/bmb/ldq023
[3] Aswad F, Kawamura H, Dennert G . High sensitivity of CD4+CD25+ regulatory T cells to extracellular metabolites nicotinamide adenine dinucleotide and ATP: a role for P2X7 receptors.[J] Immunol. 2005; 175(5):3075-3083.
doi: 10.4049/jimmunol.175.5.3075
[4] Karagöz B, Bilgi O, Gümüs M, Erikçi AA, Sayan O, Türken O, Kandemir EG, Oztürk A, Yaylaci M . CD8+CD28– cells and CD4+ CD25+ regulatory T cells in the peripheral blood of advanced stage lung cancer patients[J]. Med Oncol, 2010,27(1):29-33.
doi: 10.1007/s12032-008-9165-9
[5] Liu JC, Wang LP, Zhang L, Wang YP, Li MJ . Significance of measurement of CD4+ CD25+ Foxp3+ regulatory T cell in patients with lung cancer[J]. Zhongguo Shi Yong Yi Kan, 2009,36(8):3-5.
刘俊才, 王丽萍, 张岚, 王玉萍, 李明君 . CD4+CD25+Foxp3+调节性T细胞在肺癌患者体内检测及其意义. 中国实用医刊. 2009; 36(8):3-5.
[6] Petersen RP, Campa MJ, Sperlazza J, Conlon D, Joshi MB, Harpole DH Jr, Patz EF Jr . Tumor infiltrating Foxp3+ regulatory T-cells are associated with recurrence in pathologic stage Ⅰ NSCLC patients[J]. Cancer, 2006,107(12):2866-2872.
doi: 10.1002/(ISSN)1097-0142
[7] Shimizu K, Nakata M, Hirami Y, Yukawa T, Maeda A, Tanemoto K . Tumor-infiltrating Foxp3+ regulatory T cells are correlated with cyclooxygenase-2 expression and are associated with recurrence in resected non-small cell lung cancer[J]. J Thorac Oncol, 2010,5(5):585-590.
doi: 10.1097/JTO.0b013e3181d60fd7
[8] Granville CA, Memmott RM, Balogh A, Mariotti J, Kawabata S, Han W, Lopiccolo J, Foley J, Liewehr DJ, Steinberg SM, Fowler DH, Hollander MC, Dennis PA . A central role for Foxp3+ regulatory T cells in K-Ras-driven lung tumorigenesis[J]. PLoS One, 2009,4(3):e5061.
doi: 10.1371/journal.pone.0005061 pmid: 2659439
[9] Li H, Yu JP, Cao S, Wei F, Zhang P, An XM, Huang ZT, Ren XB . CD4+CD25+ regulatory T cells decreased the antitumor activity of cytokine-induced killer (CIK) cells of lung cancer patients. J Clin Immunol. 2007; 27(3):317-326.
[10] Sharma S, Yang SC, Zhu L, Reckamp K, Gardner B, Baratelli F, Huang M, Batra RK, Dubinett SM . Tumor cyclooxygenase-2/prostaglandin E2-dependent promotion of FOXP3 expression and CD4+ CD25+ T regulatory cell activities in lung cancer[J]. Cancer Res, 2005,65(12):5211-5220.
doi: 10.1158/0008-5472.CAN-05-0141
[11] Li X, Cui YS, Wang Y, Zheng XH, Li Y . The detection of CD4+ CD25+ Treg in mice with Lewis lung cancer and the clinical significance[J]. Xian Dai Zhong Liu Yi Xue, 2007,15(4):454-457.
doi: 10.3969/j.issn.1672-4992.2007.04.003
李欣, 崔永生, 王炎, 郑晓辉, 李一 . CD4+CD25+调节性T细胞在Lewis肺癌移植鼠中的检测及临床意义. 现代肿瘤医学. 2007; 15(4):454-457.
doi: 10.3969/j.issn.1672-4992.2007.04.003
[12] Xu ZY, Jin CJ, Zhou CC, Wang ZQ, Zhou WD, Deng HB, Zhang M, Su W, Cai XY . Treatment of advanced non-small-cell lung cancer with Chinese herbal medicine by stages combined with chemotherapy[J]. J Cancer Res Clin Oncol, 2011,137(7):1117-1122.
doi: 10.1007/s00432-011-0975-3
[13] Wang JY, Zheng Z, Wang Q, Guo J, Chen L . Antitumor mechanism preliminary studied by proteome on Feiyanning Granule against lung cancer in nude mice[J]. Zhong Liu Fang Zhi Yan Jiu, 2011,38(1):5-8.
王菊勇, 郑展, 王青, 郭净, 陈灵 . 肺岩宁冲剂抗肺癌机制的初步探讨[J]. 肿瘤防治研究, 2011,38(1):5-8.
[14] Wang JY, Jin Y, Xu ZY, Zheng Z . Effects of Feiyanning Decoction on gene expression of nuclear factor-κB activated by tumor necrosis factor-α in lung adenocarcinoma cell line[J]. J Chin Integr Med, 2009,7(3):249-254.
王菊勇, 金叶, 徐振晔, 郑展 . 肺岩宁方对肿瘤坏死因子α诱导的人肺癌细胞系核转录因子κB基因表达的影响[J]. 中西医结合学报, 2009,7(3):249-254.
[1] Jian-sheng Li, Ya Li, Su-yun Li, Yuan-yuan Wang, Li Deng, Yan-ge Tian, Su-li Jiang , Ying Wang. Long-term effects of Tiaobu Feishen therapies on systemic and local inflammation responses in rats with stable chronic obstructive pulmonary disease. Journal of Chinese Integrative Medicine, 2012, 10(9): 1039-1048.
[2] Lu Yu, Shui-miao Lin, Ru-qian Zhou, Wei-jun Tang, Pin-xian Huang, Ying Dong, Jian Wang, Zhi-hua Yu, Jiu-lin Chen, Li Wei, San-li Xing, Hui-juan Cao, Hong-bin Zhao. Chinese herbal medicine for patients with mild to moderate Alzheimer disease based on syndrome differentiation: A randomized controlled trial. Journal of Chinese Integrative Medicine, 2012, 10(7): 766-776.
[3] Ling Xu, Qiao-ling Zhou, Jie Han, Dan-ying Zhang, Hui-juan Dong, Zai-long Cai, Chao-qin Yu, Dong-xia Zhai . Effects of Chinese herbal medicine Neiyi Recipe-medicated serum on angiopoiesis of endometriosis in the chick chorioallantoic membrane model. Journal of Chinese Integrative Medicine, 2012, 10(7): 800-806.
[4] Dong-mei Zhang, Li-xia Lou, Ai-ming Wu, Xi-ying Lü, Zhao-juan Hu, Yan-hong Zhang, Hong-fang Liu. Effects of Astragalus membranaceus and Potentilla discolor mixture on insulin resistance and its related mRNA expressions in KKAy mice with type 2 diabetes. Journal of Chinese Integrative Medicine, 2012, 10(7): 821-826.
[5] Lin Wang, Guan-liang Wang, Jia-han Liu, Di Li, De-zeng Zhu, Liang-neng Wu . Effects of ursolic acid in ameliorating insulin resistance in liver of KKAy mice via peroxisome proliferator-activated receptors α and γ. Journal of Chinese Integrative Medicine, 2012, 10(7): 793-799.
[6] Mei-jiao Mao, Jun-ping Hu, Cong Wang, Yi-yi Zhang, Ping Liu. Effects of Chinese herbal medicine Guanxinkang on expression of PPARγ-LXRα-ABCA1 pathway in ApoE-knockout mice with atherosclerosis. Journal of Chinese Integrative Medicine, 2012, 10(7): 814-820.
[7] Yi-tao Zhao , Xin-guang Zhang , Li Bai , Li-qing Li , Jian-er Yu . Effects of Chinese herbal medicine Pingchuan Formula on airway inflammation, interferon-γ and interleukin-4 in mice with asthma. Journal of Chinese Integrative Medicine, 2012, 10(7): 807-813.
[8] Shui-qiu Deng, Xue-nong Ouyang, Zong-yang Yu, Xi-hu Dai, Xi Chen, Fang-zheng Fang, Wen-wu Wang, Zhi-zhen Liu. Influence of Chinese herbal medicine Feitai Capsule on completion or delay of chemotherapy in patients with stage ⅢB/Ⅳ non-small-cell lung cancer: a Randomized controlled trial. Journal of Chinese Integrative Medicine, 2012, 10(6): 635-640.
[9] Chuan Chen, Hui-ying Chi, Zhi-hua Yu, Jiu-lin Chen . Effects of Chinese herbal medicine Shoushen Granule on telomere length and telomerase activity of peripheral white blood cells and vascular cells in rats with atherosclerosis. Journal of Chinese Integrative Medicine, 2012, 10(6): 667-673.
[10] Hui Luo, Jian-ping Liu, Qing Li. Methodological issues and suggestions for improvement in randomized controlled trials of Chinese herbal medicine for recurrent miscarriage. Journal of Chinese Integrative Medicine, 2012, 10(6): 604-614.
[11] Daniel A. Weber, Janelle M. Wheat , Geoffrey M. Currie. Cancer stem cells and the impact of Chinese herbs, isolates and other complementary medical botanicals: A review. Journal of Chinese Integrative Medicine, 2012, 10(5): 493-503.
[12] Surendra Kr. Sharma, Naveen Goyal. Protective effect of Heliotropium eichwaldi against cisplatin-induced nephrotoxicity in mice. Journal of Chinese Integrative Medicine, 2012, 10(5): 555-560.
[13] Qing-lan Wang, Yan-yan Tao , Li Shen , Hong-yan Cui , Cheng-hai Liu. Chinese herbal medicine Fuzheng Huayu recipe inhibits liver fibrosis by mediating the transforming growth factor-β1/Smads signaling pathway. Journal of Chinese Integrative Medicine, 2012, 10(5): 561-568.
[14] Zhan gheng, Ju-yong Wang, Qing Wang, Ling Xu, Zhen-ye Xu. Effects of Chinese herbal medicine Feiyanning decoction on expressions of nucleosome conformation-regulating factors H3-K56, Rtt109, Asf1 and E2F1 in Lewis-bearing mice. Journal of Chinese Integrative Medicine, 2012, 10(4): 448-453.
[15] Mahmoudian Alireza, Rajaei Ziba, Haghir Hossein, Banihashemian Shahaboldin, Hami Javad. Effects of valerian consumption during pregnancy on cortical volume and the levels of zinc and copper in the brain tissue of mouse fetus. Journal of Chinese Integrative Medicine, 2012, 10(4): 424-429.
Viewed
Full text


Abstract

Cited
  Shared   
  Discussed   
[1] Dong Yang, Yong-ping Du, Qing Shen, Wei Chen, Yan Yu, Guang-lei Chen. Expression of alpha-smooth muscle actin in renal tubulointerstitium in patients with kidney collateral stasis. Journal of Chinese Integrative Medicine, 2008, 6(1): 41-44
[2] Hai-feng Wei, Bai-liu Ya, Ling Zhao, Cui-fei Ye, Li Zhang, Lin Li. Evaluation of tongue manifestation of blood stasis syndrome and its relationship with blood rheological disorder in a rat model of transient brain ischemia. Journal of Chinese Integrative Medicine, 2008, 6(1): 73-76
[3] Xi Lin, Jian-ping Liu. Herbal medicines for viral myocarditis. Journal of Chinese Integrative Medicine, 2008, 6(1): 76
[4] Xi Lin, Jian-ping Liu. Tai chi for treating rheumatoid arthritis. Journal of Chinese Integrative Medicine, 2008, 6(1): 82
[5] Liang-ping Hu, Hui Gao. Discrimination of errors in statistical analysis of medical papers published in the first issue of 2006 in Journal of Chinese Integrative Medicine. Journal of Chinese Integrative Medicine, 2008, 6(1): 98-106
[6] Yan-bo Zhu , Qi Wang, Cheng-yu Wu, Guo-ming Pang, Jian-xiong Zhao, Shi-lin Shen, Zhong-yuan Xia , Xue Yan . Logistic regression analysis on relationships between traditional Chinese medicine constitutional types and overweight or obesity. Journal of Chinese Integrative Medicine, 2010, 8(11): 1023-1035
[7] Wei Xu, Meng Shi, Jian-gang Liu, Cheng-long Wang . Collagen protein expressions in ischemic myocardium of rats with acute myocardial infarction and effects of qi-tonifying, yin-tonifying and blood-activating herbs and detoxifying and blood-activating herbs. Journal of Chinese Integrative Medicine, 2010, 8(11): 1041-1047
[8] Tao Wang , Feng Qin. Effects of Chinese herbal medicine Xiaoyao Powder on monoamine neurotransmitters in hippocampus of rats with postpartum depression. Journal of Chinese Integrative Medicine, 2010, 8(11): 1075-1079
[9] Ying Xu , Chang-chun Zeng , Xiu-yu Cai , Rong-ping Guo , Guang Nie , Ying Jin. Chromaticity and optical spectrum colorimetry of the tongue color in different syndromes of primary hepatic carcinoma. Journal of Chinese Integrative Medicine, 2012, 10(11): 1263-1271
[10] Xiang-ying Mao , Qin Bian , Zi-yin Shen. Analysis of the osteogenetic effects exerted on mesenchymal stem cell strain C3H10T1/2 by icariin via MAPK signaling pathway in vitro. Journal of Chinese Integrative Medicine, 2012, 10(11): 1272-1278
[an error occurred while processing this directive]