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Title: [Anti-tumor and immune-modulating effect of Jiawei Sijunzi decoction in mice bearing hepatoma H22 tumor].
Author: Chen L, Jin T, Ning C, Wang S, Wang L, Lin J.
Journal: Nan Fang Yi Ke Da Xue Xue Bao; 2019 Feb 28; 39(2):241-248. PubMed ID: 30890515.
Abstract:
OBJECTIVE: To investigate the antitumor activity of Jiawei Sijunzi decoction and study its liver and kidney toxicity and its effect on the immune system in a tumor-bearing mouse model. METHODS: Hepatoma H22 tumor-bearing mouse models were randomized into model group, cyclophosphamide (CTX) group, and low-, moderate-, and high-dose Jiawei Sijunzi decoction groups (JW-L, JW-M, and JW-H groups, respectively). The antitumor activity of Jiawei Sijunzi decoction was assessed by calculating the tumor inhibition rate and pathological observation of the tumor tissues. Immunohistochemistry was used to detect the expressions of Bax, Bcl-2, Bax/Bcl-2 and caspase-3 in the tumors. The liver and kidney toxicity of Jiawei Sijunzi decoction was analyzed by evaluating the biochemical indicators of liver and kidney functions. The immune function of the tumor-bearing mice were assessed by calculating the immune organ index, testing peripheral blood routines, and detection of serum IL-2 and TNF-α levels using enzyme-linked immunosorbent assay. RESULTS: Compared with that in the model group, the tumor mass in CTX, JW-M and JW-H groups were all significantly reduced (P < 0.05) with cell rupture and necrosis in the tumors. Immunohistochemistry revealed obviously up-regulated expressions of Bax and caspase-3 and down- regulated expression of Bcl-2 protein with an increased Bax/Bcl-2 ratio in CTX, JW-M and JW-H groups. Treatment with Jiawei Sijunzi decoction significantly reduced Cr, BUN, AST and ALT levels, improved the immune organ index, increased peripheral blood leukocytes, erythrocytes and hemoglobin levels, and up-regulated the levels of TNF-α and IL-2 in the tumor-bearing mice. These changes were especially significant in JW-H group when compared with the parameters in the model group (P < 0.01). CONCLUSIONS: Jiawei Sijunzi decoction has a strong anti-tumor activity and can improve the liver and kidney functions of tumor-bearing mice. Its anti-tumor effect may be attributed to the up-regulation of Bax, caspase-3, TNF-α and IL-2 levels and the down-regulation of Bcl-2 expression as well as the enhancement of the non-specific immune function. 目的: 探讨加味四君子汤的体内抑瘤活性及对肝肾毒性、免疫系统的影响。方法: 建立H22荷瘤小鼠模型，将荷瘤小鼠分为空白组、模型组、环磷酰胺组、加味四君子汤低、中、高剂量组。通过计算抑瘤率，观察肿瘤组织HE染色病理切片，免疫组化法检测Bax、Bcl-2、Bax/Bcl-2及caspase-3水平研究加味四君子汤的抑瘤活性及相关机制；通过肝肾生化指标观察加味四君子汤的肝肾毒性；通过计算荷瘤小鼠免疫器官指数、外周血检测血常规和酶联免疫法检测小鼠血清的IL-2、TNF-α的水平探讨加味四君子汤对H22荷瘤小鼠免疫功能的影响。结果: 环磷酰胺组、加味四君子汤中剂量、高剂量组的肿瘤质量均低于模型组（P < 0.05），抑瘤活性差异均有统计学意义；其肿瘤细胞有不同程度的破裂坏死，免疫组化各实验组能有效上调Bax和caspase-3蛋白表达，下调Bcl-2蛋白表达，提高Bax/Bcl-2比值。同时，加味四君子汤降低了荷瘤小鼠的Cr、BUN、AST与ALT水平，提高了免疫器官指数和外周血白细胞、红细胞和血红蛋白含量，上调了TNF-α、IL-2水平，其中，高剂量组与模型组差异具有统计学意义（P < 0.01）。结论: 加味四君子汤具有较好的体内抑瘤活性，能改善荷瘤小鼠的肝肾功能，其抑瘤作用可能与上调Bax、caspase-3表达、TNF-α和IL-2水平，下调Bcl-2蛋白表达以及增强小鼠的非特异性免疫功能有关。

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