摘要
目的:采用临床队列、网络药理学框架及分子对接技术阐明复方苦参注射液(CKI)协同索拉非尼治疗晚期肝细胞癌(HCC)的物质基础和分子机制。方法:依据入组标准选取安徽医科大学附属六安医院2019年7月至2022年6月间治疗的134例晚期HCC患者,其中CKI-索拉非尼组和索拉非尼组各67例。分析两组患者应答率和总体生存率。通过网络药理学框架结合中药系统药理学数据库与分析平台及Gene Cards、OMIM,Pharm Gkb、TTD和Drug Bank数据库鉴定CKI治疗晚期HCC的靶基因。通过酶联免疫吸附测定验证两组患者治疗前后FBJ骨髓瘤病毒癌基因同源物(FOS)和表皮生长因子受体(EGFR)表达。结果:CKI-索拉非尼组患者治疗应答率和生存率均高于索拉非尼组患者(应答率:74.6%∶66.2%,P=0.032;生存率:38.8%∶23.9%,P=0.013)。FOS和EGFR是CKI治疗晚期HCC的核心靶基因。治疗3个月后,CKI-索拉非尼组患者外周血FOS和EGFR浓度较索拉非尼组患者显著降低[FOS浓度:(8.41±2.17)ng/ml∶(9.85±2.47)ng/ml,P<0.001;EGFR浓度:(5.47±2.14)ng/ml∶(6.28±2.04)ng/ml,P=0.027]。分子对接模型证实槲皮素能与FOS和EGFR相互作用,结合能分别为-8.2 kcal/mol和-7.9 kcal/mol。结论:CKI协同索拉非尼提高晚期HCC患者应答率和生存率,其FOS和EGFR是介导其应答的潜在机制。
Objective:Clinical cohort,network pharmacological framework and molecular docking techniques were used to elucidate the material basis and molecular mechanism of compound compound kushen injection(CKI)synergising with sorafenib in the treatment of advanced hepatocellular carcinoma(HCC).Methods:A total of 134 patients with advanced HCC treated in our hospital between July 2019 and June 2022,including 67 patients in the CKI-sorafenib group and 67 patients in the sorafenib group,were selected to analyse the response rate and overall survival rate of patients in both groups.The CKI anti-advanced HCC target genes were identified by a web-based pharmacological framework combined with the Traditional Chinese Medicine Systematic Pharmacology Database and Analysis Platform and GeneCards,OMIM,PharmGkb,TTD or DrugBank databases.The expression of FBJ murine osteosarcoma viral oncogene homolog(FOS)and epidermal growth factor receptor(EGFR)was verified by enzyme-linked immunosorbent assay before and after treatment in both groups.Results:The treatment response rate and survival rate of patients in the CKI-sorafenib group were higher than those in the sorafenib group(response rate:74.6%vs.66.2%,P=0.032;survival rate:38.8%vs.23.9%,P=0.013).FOS and EGFR are the core target genes of CKI against advanced HCC.After 3 months of treatment,peripheral blood FOS and EGFR concentrations were significantly lower in patients in the CKI-sorafenib group compared with those in the sorafenib group(FOS:(8.41±2.17)ng/ml vs.(9.85±2.47)ng/ml,P<0.001;EGFR:(5.47±2.14)ng/ml vs.(6.28±2.04)ng/ml,P=0.027).Molecular docking modelling fraction confirmed that quercetin could interact with FOS and EGFR with binding energies of-8.2 kcal/mol and-7.9 kcal/mol,respectively.Conclusion:CKIs synergise with sorafenib to increase response rates and improve survival time in patients with advanced HCC,with FOS and EGFR as potential mechanisms mediating their response.
作者
李先晨
徐秋燕
盛文飞
李栋梁
吴庆庆
陶忠义
Li Xianchen;Xu Qiuyan;Sheng Wenfei;Li Dongliang;Wu Qingqing;Tao Zhongyi(Department of Pharmacy,Lu'an Hospital of Anhui Medical University,Lu'an 237000,Anhui,China;Medical Oncology,Lu'an Hospital of Anhui Medical University,Lu'an 237000,Anhui,China;General Surgery,Lu'an Hospital of Anhui Medical University,Lu'an 237000,Anhui,China)
出处
《肝癌电子杂志》
2023年第4期42-50,共9页
Electronic Journal of Liver Tumor
基金
安徽省自然科学基金(2022kykt32)。
关键词
晚期肝细胞癌
复方苦参注射液
网络药理学
分子对接
索拉非尼
Advanced hepatocellular carcinoma
Compound kushen injection
Network pharmacology
Molecular docking
Sorafenib
作者简介
通信作者:陶忠义,Emmail:13956111426@139.com。
