Chen Zhonghua, Liu Mei, Xie Kaiyong, Chen Haitao, Wang Jun, Liu Xing
Key Laboratory of Drug-Targeting and Drug Delivery System of the Education Ministry, Sichuan Engineering Laboratory for Plant-Sourced Drug and Sichuan Research Center for Drug Precision Industrial Technology, West China School of Pharmacy, Sichuan University, Chengdu 610041, China.
Department of Pharmacology, West China School of Pharmacy, Sichuan University, Chengdu 610041, China.
Transl Cancer Res. 2019 Nov;8(7):2602-2612. doi: 10.21037/tcr.2019.10.25.
This study aimed to investigate the anti-tumor effects of Huisheng Oral Solution (HSOS) on the promotion of blood circulation to dispel blood stasis, the inhibition of metastasis and inflammation, the pathogenesis of tumor progression, and to provide guidelines for using HSOS in clinical settings.
Eight-month-old Lewis lung carcinoma (LLC)-bearing CBL/6 mice were orally administered HSOS (0.25 mL/d) for 21 d starting on day 2 of model generation. One hour after the final administration, their eyeballs were dissected out to collect serum to determine tissue factor (TF) and interleukin-6 (IL-6) levels via ELISA. Blood was collected intracardially with an anticoagulant to determine fibrinogen levels, using an automated blood coagulation analyzer. The mice were euthanized via cervical dislocation and their thymi, spleens, and tumors were extracted for weight measurement and organ index calculation. CD44 and MMP2 expression and VEGF protein and mRNA expression in tumor tissues were detected using immunohistochemical (IHC) and RT-qPCR assays, respectively. Lastly, the effect of HSOS on the migration ability of A549 lung carcinoma cells was investigated using scratch assay.
HSOS significantly downregulated TF and Fib in tumor-bearing mice. HSOS inhibited the overexpression of CD44, MMP2, and VEGF, and the migration ability of tumor cells. Moreover, the pro-inflammatory cytokine (IL-6) was significantly downregulated, but the thymic and splenic indices increased.
HSOS might exert anti-tumor effects by improving hypercoagulability in tumor-bearing mice, inhibiting tumor cell metastasis, alleviating inflammatory responses, and enhancing immune function.
本研究旨在探讨回生口服液（HSOS）在促进血液循环以消散瘀血、抑制转移和炎症以及肿瘤进展发病机制方面的抗肿瘤作用，并为其在临床中的应用提供指导。
从模型建立第2天开始，对8月龄携带Lewis肺癌（LLC）的C57BL/6小鼠口服给予HSOS（0.25 mL/d），持续21天。末次给药1小时后，摘除眼球收集血清，通过酶联免疫吸附测定（ELISA）法测定组织因子（TF）和白细胞介素-6（IL-6）水平。用抗凝剂经心脏采血，使用自动血液凝固分析仪测定纤维蛋白原水平。通过颈椎脱臼法对小鼠实施安乐死，取出胸腺、脾脏和肿瘤进行称重并计算器官指数。分别采用免疫组织化学（IHC）和逆转录定量聚合酶链反应（RT-qPCR）检测肿瘤组织中CD44和基质金属蛋白酶2（MMP2）的表达以及血管内皮生长因子（VEGF）蛋白和信使核糖核酸（mRNA）的表达。最后，采用划痕试验研究HSOS对A549肺癌细胞迁移能力的影响。
HSOS显著下调荷瘤小鼠的TF和纤维蛋白原（Fib）水平。HSOS抑制CD44、MMP2和VEGF的过表达以及肿瘤细胞的迁移能力。此外，促炎细胞因子（IL-6）显著下调，但胸腺和脾脏指数增加。
HSOS可能通过改善荷瘤小鼠的高凝状态、抑制肿瘤细胞转移、减轻炎症反应和增强免疫功能发挥抗肿瘤作用。
