消岩汤对Lewis肺癌小鼠的抑瘤作用及对髓源性抑制细胞的影响

Effect of Xiaoyan Decoction on tumor inhibition and myeloid-derived suppressor cells of mice with Lewis lung cancer

关键词:  消岩汤  髓源性抑制细胞  肺癌  中医药

Key words:  Xiaoyan Decoction  myeloid-derived suppressor cells  lung cancer  traditional Chinese medicine

摘要:

[目的] 观察消岩汤对Lewis肺癌小鼠肿瘤生长的抑制作用及对髓源性抑制细胞（MDSCs）的影响。[方法] 选取C57BL/6小鼠建立Lewis肺癌小鼠模型。成模小鼠随机分为模型组、环磷酰胺（CTX）组、消岩汤组、联合组，每组6只。另取正常小鼠6只为空白组。空白组、模型组：每日灌胃0.2 mL生理盐水；消岩汤组：每日予消岩汤灌胃2次，每次0.2 mL（28.77 g/mL）；环磷酰胺组：每日腹腔注射CTX 0.2 mL（6 mg/mL）；联合组：在消岩汤组基础上腹腔注射CTX 0.2 mL（6 mg/mL）。7 d后处死小鼠，称量瘤质量、脾脏质量、胸腺质量，计算抑瘤率、脾指数、胸腺指数。流式细胞技术检测小鼠脾脏MDSCs表达水平，酶联免疫吸附（ELISA）法检测小鼠外周血白细胞介素（IL）-6，转化生长因子-β（TGF-β）表达水平。[结果] 各组小鼠抑瘤率结果表明，消岩汤、环磷酰胺及联合用药干预均可抑制肿瘤生长，抑瘤率分别为20.3%、49.7%及56.7%。与模型组比较，消岩汤组及联合组脾指数及胸腺指数显著升高（P<0.05）。与空白组相比，模型组小鼠脾脏中MDSCs百分比显著上升（P<0.05）；与模型组比较，消岩汤组、CTX组及联合组小鼠脾脏中MDSCs百分比均有不同程度显著降低（P<0.05）；与CTX组相比，联合组小鼠脾脏中MDSCs百分比降低更显著（P<0.05）。与模型组相比，消岩汤组、CTX组及联合组小鼠血清中IL-6、TGF-β水平有不同程度降低（P<0.05）；与CTX组相比，联合组小鼠血清中TGF-β水平显著降低（P<0.05）。[结论] 消岩汤可以协同化疗药物抑制肿瘤生长，下调免疫负向调节因子IL-6、TGF-β水平，抑制MDSCs扩增，可能从重塑肿瘤免疫微环境角度发挥作用。

Abstract:

[Objective] To observe the inhibitory effect of Xiaoyan Decoction on tumor growth in Lewis lung cancer mice and the effect on myeloid-derived suppressor cells (MDSCs).[Methods] C57BL/6 mice were selected to establish Lewis lung cancer mouse model. The model mice were randomly divided into model group,cyclophosphamide (CTX) group,Xiaoyan Decoction group and combination group,with 6 mice in each group. Another 6 normal mice were selected as blank group. Blank group and model group:daily gavage 0.2 mL normal saline;Xiaoyan Decoction group:Xiaoyan Decoction was gavaged twice a day,0.2 mL (28.77 g/mL) each time;CTX group:daily intraperitoneal injection of CTX 0.2 mL (6 mg/mL);Combination group:CTX 0.2 mL (6 mg/mL) was intraperitoneally injected on the basis of Xiaoyan Decoction group. After 7 days,the mice were sacrificed,and the tumor weight,spleen weight and thymus weight were weighed,the tumor inhibition rate,spleen index and thymus index were calculated. The expression level of MDSCs in the spleen of mice was detected by flow cytometry,and the expression levels of IL-6 and TGF-β in the peripheral blood of mice was detected by Elisa.[Results] Xiaoyan Decoction,CTX and the combination of drugs could inhibit tumor growth,and the tumor inhibition rates were 20.3%,49.7% and 56.7%,respectively.Compared with the model group,the spleen index and thymus index of Xiaoyan Decoction group and the combination group were significantly increased (P<0.05). Compared with the blank group,MDSCs percentage in the spleen of the model group increased significantly (P<0.05),while compared with the model group,the percentages of MDSCs in spleen of mice in Xiaoyan Decoction group,CTX group and combination group were significantly reduced to different degrees (P<0.05). Compared with CTX group,the percentage of MDSCs in spleen of mice in combination group was significantly reduced (P<0.05). Compared with the model group,serum levels of IL-6 and TGF-β were decreased in mice of Xiaoyan Decoction group,CTX group and combination group to varying degrees (P<0.05). Compared with the CTX group,the serum levels of TGF-β in mice in the combination group were significantly lower (P<0.05).[Conclusion] Xiaoyan Decoction can cooperate with chemotherapy drugs to inhibit tumor growth,down-regulate the levels of negative immune regulators IL-6 and TGF-β expression,inhibit the proliferation of MDSCs,which may play a role in reshaping tumor immune microenvironment.