|
|
Experimental study on antitumor effect and the effect of tumor immune microenvironment of Yanghe Decoction on Lewis lung cancer mice |
WU Lin1 ZHANG Weibo2 XING Yanli1 LI Yan1 ZHAO Meifeng1 YAO Huan1 |
1.Department of Pharmacy, Xianyang Central Hospital, Shaanxi Province, Xianyang 712000, China;
2.Department of Pathology, Xianyang Central Hospital, Shaanxi Province, Xianyang 712000, China |
|
|
Abstract Objective To investigate the antitumor effect and the effect of tumor immune microenvironment of Yanghe Decoction on Lewis lung cancer mice. Methods A total of 50 male C57BL/6 mice were subcutaneously inoculated with 0.2 ml Lewis lung cancer cell suspension at the concentration of 2×107/ml in the right anterior axilla to establish Lewis lung cancer mouse model. After the model was made, according to random number table method, these mice were divided into tumor-bearing model group, Cyclophosphamide group, Yanghe Decoction high concentration group, Yanghe Decoction medium concentration group, and low concentration group, with 10 mice in each group. Normal saline, 25 mg/kg Cyclophosphamide, 27.5, 18.3, and 9.2 g/kg Yanghe Decoction were given by intragastric administration for 10 days, respectively, one time per day. The body weight and tumor weight of mice in each group were observed. The expressions of interleukin (IL)-2, transforming growth factor (TGF)-β, and cytotoxic lymphocyte (CTL) and regulatory T cell (Treg) markers CD3+CD8+ CD4+Foxp3+ in tumor tissues were detected by immunohistochemistry and immunofluorescence, respectively. Results Compared with tumor-bearing model group, the body weight of mice in Yanghe Decoction high, medium concentration groups were increased (P < 0.05 or P < 0.01); compared with Cyclophosphamide group, the body weight of mice in Yanghe decoction high, medium, and low concentration groups were increased (P < 0.01); and compared with Yanghe Decoction high concentration group, the body weight of mice in Yanghe Decoction low concentration group was decreased (P < 0.05). Compared with tumor-bearing model group, tumor weight of mice in Yanghe Decoction high concentration group was decreased (P < 0.05); and compared with Cyclophosphamide group, tumor weight of mice in Yanghe Decoction medium, low concentration groups were increased (P < 0.05). The tumor inhibition rate from high to low was Cyclophosphamide group, Yanghe Decoction high concentration group, Yanghe Decoction medium concentration group and Yanghe Decoction low concentration group. Compared with tumor-bearing model group, the expression of IL-2 in Lewis lung cancer tissues of mice in Yanghe Decoction high, medium, and low concentration groups were increased (P < 0.05 or P < 0.01); compared with Cyclophosphamide group, the expression of IL-2 in Lewis lung cancer tissues of mice in Yanghe Decoction high, medium, and low concentration groups were increased (P < 0.01); and compared with Yanghe Decoction high concentration group, the expression of IL-2 in Lewis lung cancer tissues of mice in Yanghe Decoction medium, low concentration were decreased (P < 0.01). Compared with tumor-bearing model group, the expression of TGF-β in Lewis lung cancer tissue of mice in Yanghe Decoction high, medium concentration groups were decreased (P < 0.01); compared with Cyclophosphamide group, the expression of TGF-β in Lewis lung cancer tissues of mice in Yanghe Decoction medium, low concentration groups were increased (P < 0.05). Compared with tumor-bearing model group, the expression of CD3+CD8+ in Lewis lung cancer tissues of mice in Yanghe Decoction high, medium, and low concentration groups were increased (P < 0.05 or P < 0.01); compared with Cyclophosphamide group, the expression of CD3+CD8+ in Lewis lung cancer tissues of mice in Yanghe Decoction high, medium, and low concentration groups were increased (P < 0.01); and compared with Yanghe Decoction high concentration group, the expression of CD3+CD8+ in Lewis lung cancer tissues of mice in Yanghe Decoction medium, low concentration were decreased (P < 0.01). Compared with tumor-bearing model group, the expression of CD4+Foxp3+ in Lewis lung cancer tissues of mice in Yanghe Decoction high, medium concentration groups were decreased (P < 0.05 or P < 0.01). Conclusion Yanghe Decoction has a good anti-tumor effect on Lewis lung cancer mice without affecting their body weight, can increase the expression of IL-2 and CTL content in tumor immune microenvironment, and reduce the expression of TGF-β and the content of Treg in tumor immune microenvironment.
|
|
|
|
|
[1] 清·王维德撰,胡晓峰.外科证治全生集[M].北京:人民卫生出版社,2006:1-16.
[2] 邓芳柏,赵小青,刘良.温阳解凝之阳和汤治疗肺癌浅析[J].中医药通报,2006,5(3):23-26.
[3] 陶芬芬,赵厚睿.阴疽证治理论的临床应用探讨[J].江西中医药,2019,50(437):19-21.
[4] 王新新,田同德,杨亚琴.阳和汤抗肿瘤的研究进展[J].中国中医药现代远程教育,2015,13(20):156-157.
[5] 张秋菊,李能莲,张立,等.阳和汤治疗恶性肿瘤评述[J].河南中医,2018,38(7):1132-1134.
[6] 叶峥嵘,杨晓航,吴琳.阳和汤治疗肿瘤的临床应用与实验研究进展[J].陕西中医学院学报,2011,34(4):90-93.
[7] 姚嘉良,安君君,杨亚琴.阳和汤治疗恶性肿瘤的临床应用与实验研究进展[J].中国中医药现代远程教育,2018, 16(11):156-158.
[8] 彭吉勇.阳和汤治疗恶性肿瘤的临床应用规律研究[D].长沙:湖南中医药大学,2010.
[9] Junttila MR,Sauvage FJD. Influence of tumour micro-environment heterogeneity on therapeutic response [J]. Nature,2013,501(7467):346-354.
[10] Fridman WH,Zitvogel L,Sautès-Fridman C,et al. The immune contexture in cancer prognosis and treatment [J]. Nat Rev Clin Oncol,2017,14(12):717-734.
[11] 俞文峰,牛越群,吕望,等.中医药在肿瘤免疫微环境中的作用[J].浙江中西医结合杂志,2019,29(8):695-698.
[12] 杨娜,吴琳,刘晓彤,等.中医药调节肿瘤免疫微环境研究进展[J].辽宁中医药大学学报,2019,21(8):164-167.
[13] Fidler IJ. The pathogenesis of cancer metastasis:the“seed and soil”hypothesis revisited [J]. Nat Rev Cancer,2003, 3(6):453-458.
[14] van Kempen LC,Ruiter DJ,van Muijen GN,et al. The tumor microenvironment:a critical determinant of neoplastic evolution [J]. Eur J Cell Biol,2003,82(11):539-548.
[15] 杨芳,于雁.肿瘤微环境——肿瘤转移的关键因素[J].中国肺癌杂志,2015,18(1):48-54.
[16] Sung SY,Hsieh CL,Wu D,et al. Tumor microenvironment promotes cancer progression,metastasis,and therapeutic resistance [J]. Curr Probl Cancer,2007,31(2):36-100.
[17] Wu T,Dai Y. Tumor microenvironment and therapeutic response [J]. Cancer Lett,2017,387:61-68. DOI:10.1016/j.canlet.2016.01.043.
[18] Bierie B,Moses HL. Tumour microenvironment:TGFbeta:the molecular Jekyll and Hyde of cancer [J]. Nat Rev Cancer,2006,6(7):506-520.
[19] 胡洋,夏冰,张翼鷟.外泌体在血液肿瘤免疫微环境中的作用研究进展[J].中国实验血液学杂志,2020,28(6):2084-2088.
[20] 曹雪涛.医学免疫学[M].6版.北京:人民卫生出版社,2013:176-177.
[21] Gruenbacher G,Gander H,Nussbaumer O,et al. IL-2 costimulation enables statin-mediated activation of human NK cells,preferentially through a mechanism involving CD56+ dendritic cells [J]. Cancer Res,2010,70(23):9611-9620.
[22] Yang H,Cheng EY,Sharma VK,et al. Dendritic cells with TGF-β1 and IL-2 differentiate naive CD4+ T cells into alloantigen-specific and allograft protective Foxp3+ regulatory T cells [J]. Transplantation,2012,93(6):580-588.
[23] Wilezynski JR,Radwan M,Kalinka J. The characterization and role of regulatory T cells in immune reactions [J]. Front Biosei,2008,13:2266-2274.
[24] Liu C,Workman CJ,Vignali DA. Targeting regulatory T cells in tumors [J]. Febs J,2016,283:2731.
[25] Peng Y,Laouar Y,Li MO,et al. TGF-beta regulates in vivo expansion of Foxp3-exp ressing CD4+CD25+ regulatory T cells responsible for protection against diabetes [J]. Proc Natl Acad Sci U S A,2004,101(13):4572-4577. |
|
|
|