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靶向药物联合应用对肝癌细胞SK-Hep-1增殖的影响及其机制
引用本文:朱晓霞,贾瑜琦,刘畅,弓韬,李高鹏,张宏伟,于保锋.靶向药物联合应用对肝癌细胞SK-Hep-1增殖的影响及其机制[J].肿瘤防治研究,2022,49(11):1126-1133.
作者姓名:朱晓霞  贾瑜琦  刘畅  弓韬  李高鹏  张宏伟  于保锋
作者单位:1. 030001 太原,山西医科大学基础医学院生物化学与分子生物学教研室;2. 046000 长治,长治医学院基础部生物化学与分子生物学教研室;3. 030006 太原,山西白求恩医院普通外科;4. 030013 太原,山西省肿瘤医院血液科
基金项目:国家自然科学基金(30901821, 81172 1 3 6 );山西省自然科学基金(201701D121165, 201901D111190) ; 山西青年科技研究基金(201801D221069);山西省回国留学人员科研资助项目(2020-194, 2021-165);细胞生理学教育部重点实验室(山西医科大学)开放基金(KLMEC/SXMU-202011);山西省“1331工程”重点学科建设计划项目(1331KSC);山西省优秀青年基金(201901D211547);山西省卫生健康委科研课题(2019059);“136”院级开放基金(2021YZ03)
摘    要:目的 探讨靶向药物联合应用对多驱动基因调控增殖的肝癌细胞SK-Hep-1的影响及作用机制。方法 利用对肝癌细胞SK-Hep-1敏感的靶向药物(HG6-64-1、dasatinib、crizotinib、sunitinib)绘制单靶点动力学分析曲线和双相分析曲线,对SK-Hep-1细胞进行动力学分析;Western blot法检测这些靶向药物对SK-Hep-1细胞关键信号通路的影响;MTT法检测这些药物单用和联合应用对SK-Hep-1细胞增殖的影响。结果 与单靶点动力学分析曲线比较,双相分析曲线可更好拟合靶向药物对肝癌细胞SK-Hep-1的影响,并且预测出HG6-64-1、dasatinib和MK-2206三药联合应用能有效抑制SK-Hep-1细胞增殖。结论 双相动力学分析可以更好地定量描述多驱动增殖的肝癌细胞SK-Hep-1对靶向治疗的反应,联合使用HG6-64-1、dasatinib和MK-2206是治疗肝癌潜在的药物组合。

关 键 词:肝细胞癌  双相动力学分析  多驱动增殖  靶向药物  作用机制  药物联合  
收稿时间:2022-02-23

Effects and Mechanisms of Combined Application of Molecular Targeted Drugs on Proliferation of Hepatocellular Carcinoma SK-Hep-1 Cells
ZHU Xiaoxia,JIA Yuqi,LIU Chang,GONG Tao,LI Gaopeng,ZHANG Hongwei,YU Baofeng.Effects and Mechanisms of Combined Application of Molecular Targeted Drugs on Proliferation of Hepatocellular Carcinoma SK-Hep-1 Cells[J].Cancer Research on Prevention and Treatment,2022,49(11):1126-1133.
Authors:ZHU Xiaoxia  JIA Yuqi  LIU Chang  GONG Tao  LI Gaopeng  ZHANG Hongwei  YU Baofeng
Affiliation:1. Department of Biochemistry and Molecular Biology, Basic Medical College, Shanxi Medical University, Taiyuan 030001, China; 2. Department of Biochemistry and Molecular Biology, Changzhi Medical College, Changzhi 046000, China; 3. General Surgery Department, Shanxi Bethune Hospital, Taiyuan 030006, China; 4. Department of Hematology, Shanxi Cancer Hospital, Taiyuan 030013, China
Abstract:Objective To study the effects and mechanisms of molecular targeted drug combination on multidriven proliferation hepatocellular carcinoma SK-Hep-1 cells. Methods Four molecular targeted drugs (HG6-64-1, Dasatinib, Crizotinib, and Sunitinib) were used to treat SK-Hep-1 cells, and the monophasic kinetic analysis curve and two-phase analysis curve were drawn. Western blot analysis was used to detect the effects of the above drugs on key signaling pathways in SK-Hep-1 cells. MTT assay was used to detect the effects of the above drugs and their combination on the proliferation of SK-Hep-1 cells. Results Compared with the monophasic kinetic analysis curve, the biphase analysis curve could better fit the effects of molecular targeted drugs on SK-Hep-1 cells, which predicted that the combination of HG6-64-1, Dasatinib, and MK-2206 could effectively inhibit the proliferation of SK-Hep-1 cells. Conclusion Two-phase kinetic analysis can quantitatively describe the response of multi-driven proliferation hepatocellular carcinoma SKHep-1 cells to molecular targeted therapy. The combination of HG6-64-1, Dasatinib, and MK-2206 is a potential drug combination for the treatment of hepatocellular carcinoma.
Keywords:Hepatocellular carcinoma  Two-phase dynamics analysis  Multi-driven proliferation  Molecular targeted drug  Mechanism of action  Drug combination  
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