益气化瘀解毒方对人肝癌细胞MHCC97—H迁移能力及趋化因子CXCL12、CXCR4、CXCR7表达的影响

郜文辉 曾普华 黄惠勇 叶书林 潘敏求 周芳 李为 刘丹

摘要：目的 观察益气化瘀解毒方对人肝癌细胞MHCC97-H迁移能力及趋化因子CXCL12、CXCR4、CXCR7表达的影响，探讨其相关作用机制。方法 以索拉非尼为阳性对照，CCK-8法测定益气化瘀解毒方及索拉非尼对MHCC97-H细胞增殖的作用及最佳作用浓度，划痕实验观察MHCC97-H细胞迁移能力；Western blot检测药物干预24 h后CXCL12、CXCR4、CXCR7的蛋白表达。结果 益气化瘀解毒方及索拉非尼均能抑制MHCC97-H细胞生长，24 h半数抑制浓度分别为0.095 g/mL、10 μmol/mL；益气化瘀解毒方及索拉非尼均有抑制MHCC97-H迁移的能力；经益气化瘀解毒方干预后，MHCC9-H细胞CXCL12、CXCR4、CXCR7蛋白表达量均下降。结论 益气化瘀解毒方能抑制MHCC97-H细胞增殖及迁移，其机制可能是通过下调CXCL12/CXCR4/CXCR7趋化因子轴发挥作用。

关键词：益气化瘀解毒方；索拉非尼；人肝癌细胞MHCC97-H；趋化因子

DOI：10.3969/j.issn.1005-5304.2018.07.010

中图分类号：R285.5 文献标识码：A 文章编号：1005-5304（2018）07-0041-03

Abstract： Objective To study the effects of Yiqi Huayu Jiedu Prescription on the migration ability of MHCC97-H and the expressions of CXCL12， CXCR4 and CXCR7； To discuss its relevant mechanism of action. Methods Setting Sorafenib as a positive control， CCK-8 method was used for determining the effects of Yiqi Huayu Jiedu Prescription on the cell proliferation of MHCC97-H and the optimum concentration. Scratch assay was used to observe the migration ability of MHCC97-H. The protein expressions of CXCL12， CXCR4 and CXCR7 were detected by Western blot after 24 h of medicine intervention. Results Yiqi Huayu Jiedu Prescription and Sorafenib can inhibit the cell proliferation of MHCC97-H ， and the inhibitory concentration was 0.095 g/mL and 10 μmol/mL at 24 hours. Yiqi Huayu Jiedu Prescription can inhibit migration ability of MHCC97-H. The protein expressions of CXCL12， CXCR4 and CXCR7 in hepatocellular carcinoma cells decreased after the action of Yiqi Huayu Jiedu Prescription. Conclusion Yiqi Huayu Jiedu Prescription can inhibit MHCC97-H cell proliferation and migration， which may be realized by down-regulating chemokine axis of CXCL12/CXCR4/CXCR7.

Keywords： Yiqi Huayu Jiedu Prescription； Sorafenib； MHCC97-H； chemokines

原发性肝癌（以下简称“肝癌”）具有起病隐匿、高度恶性、进展快、预后差和死亡率高等特点。目前临床上肝癌存在大多伴有肝病背景、治疗缺乏针对性、难治性耐药和源头创新药物少等问题。中药复方配伍具有多活性成分、多环节、多靶点的抗肿瘤特点，因此，从中医药寻求多靶点抗肝癌新药可望带来新的突破。本课题组前期研究显示，益气化瘀解毒方可调节免疫、稳定瘤体、抗侵袭转移，对肝癌低氧诱导因子-1α（hypoxia inducible factor-1α，HIF-1α）信号通路、肿瘤血管微环境等均有调节作用[1-6]。在前期研究的基础上，本实验观察益气化瘀解毒方对人肝癌细胞MHCC97-H细胞增殖、细胞迁移及趋化因子CXCL12、CXCR4、CXCR7表達的影响，探讨其相关作用机制。……