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半枝莲提取物通过下调荷肝癌H22小鼠的调节性T细胞并调控Th1/Th17免疫反应来抑制肿瘤生长。

Scutellaria barbata D. Don extract inhibits the tumor growth through down-regulating of Treg cells and manipulating Th1/Th17 immune response in hepatoma H22-bearing mice.

作者信息

Kan Xuefeng, Zhang Wanli, You Ruxu, Niu Yanfeng, Guo Jianrong, Xue Jun

机构信息

Department of Radiology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, 1277 Jiefang Road, Wuhan, 430022, China.

Cancer Center, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, 1277 Jiefang Road, Wuhan, 430022, China.

出版信息

BMC Complement Altern Med. 2017 Jan 13;17(1):41. doi: 10.1186/s12906-016-1551-9.

Abstract

BACKGROUND

Previous studies showed Scutellaria barbata D. Don extract (SBE) is a potent inhibitor in hepatoma and could improve immune function of hepatoma H22-bearing mice. However, the immunomodulatory function of SBE on the tumor growth of hepatoma remains unclear. This study aimed to investigate the anti-tumor effects of SBE on hepatoma H22-bearing mice and explore the underlying immunomodulatory function.

METHODS

The hepatoma H22-bearing mice were treated by SBE for 30 days. The effect of SBE on the proliferation of HepG2 cells in vitro, the growth of transplanted tumor, the cytotoxicity of natural killer (NK) cells in spleen, the amount of CD4CD25Foxp3 Treg cells and Th17 cells in tumor tissue, and the levels of IL-10, TGF-β, IL-17A, IL-2, and IFN-γ in serum of the hepatoma H22-bearing mice was observered. IL-17A was injected to the SBE treated mice from day 9 post H22 inoculation to examine its effect on tumor growth.

RESULTS

SBE treatment inhibited the proliferation of HepG2 cells in vitro with a dose-dependent manner and significantly suppressed the tumor growth of hepatoma H22-bearing mice. Meanwhile, it increased NK cells' cytotoxicity in spleen, down-regulated the amount of CD4CD25Foxp3 Treg cells and Th17 cells in tumor tissue, and decreased IL-10, TGF-β, and IL-17A levels (P < 0.01) whereas increased IL-2 and IFN-γ levels (P < 0.01) in the serum of hepatoma H22-bearing mice. Moreover, administration of recombinant mouse IL-17A reversed the anti-tumor effects of SBE.

CONCLUSION

SBE could inhibit the proliferation of HepG2 cells in vitro. Meanwhile, SBE also could inhibit the growth of H22 implanted tumor in hepatoma H22-bearing mice, and this function might be associated with immunomodulatory activity through down-regulating of Treg cells and manipulating Th1/Th17 immune response.

摘要

背景

先前的研究表明半枝莲提取物(SBE)是一种有效的肝癌抑制剂,并且可以改善荷肝癌H22小鼠的免疫功能。然而,SBE对肝癌肿瘤生长的免疫调节功能仍不清楚。本研究旨在探讨SBE对荷肝癌H22小鼠的抗肿瘤作用,并探索其潜在的免疫调节功能。

方法

用SBE处理荷肝癌H22小鼠30天。观察SBE对体外HepG2细胞增殖、移植瘤生长、脾脏自然杀伤(NK)细胞的细胞毒性、肿瘤组织中CD4CD25Foxp3调节性T细胞(Treg细胞)和辅助性T细胞17(Th17细胞)数量以及荷肝癌H22小鼠血清中白细胞介素10(IL-10)、转化生长因子-β(TGF-β)、白细胞介素17A(IL-17A)、白细胞介素2(IL-2)和干扰素-γ(IFN-γ)水平的影响。从接种H22后第9天开始向经SBE处理的小鼠注射IL-17A,以检测其对肿瘤生长的影响。

结果

SBE处理以剂量依赖的方式抑制体外HepG2细胞的增殖,并显著抑制荷肝癌H22小鼠的肿瘤生长。同时,它增加了脾脏NK细胞的细胞毒性,下调了肿瘤组织中CD4CD25Foxp3 Treg细胞和Th17细胞的数量,并降低了荷肝癌H22小鼠血清中IL-10、TGF-β和IL-17A的水平(P<0.01),而增加了IL-2和IFN-γ的水平(P<0.01)。此外,给予重组小鼠IL-17A可逆转SBE的抗肿瘤作用。

结论

SBE可在体外抑制HepG2细胞的增殖。同时,SBE还可抑制荷肝癌H22小鼠体内H22移植瘤的生长,且该功能可能与通过下调Treg细胞和调控Th1/Th17免疫反应的免疫调节活性有关。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/fd38/5237169/464a40feec47/12906_2016_1551_Fig1_HTML.jpg

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