基于网络药理学及实验验证探讨仙茅对非小细胞肺癌顺铂增敏作用机制OA北大核心CSTPCD
Exploration of the mechanism of curculiginis rhizoma sensitizing cisplatin in non-small cell lung cancer based on network pharmacology and experimental verification
目的:探讨中药仙茅对肺癌细胞顺铂化疗的增敏作用机制.方法:运用网络药理学和分子对接技术筛选仙茅对非小细胞肺癌的主要凋亡蛋白;CCK-8法检测细胞增殖率;蛋白印迹法检测仙茅、顺铂单用及联用后肺癌细胞(A549)中Caspase3和Caspase9蛋白表达量;流式细胞术检测细胞总凋亡率;细胞划痕和细胞侵袭实验检测细胞迁移和侵袭能力.结果:100~1 500 μg/mL剂量浓度的仙茅水提液对A549细胞增殖率无明显抑制作用,联用组较顺铂单用组对A549细胞的抑制作用显著增强;与对照组相比,仙茅组、联用组Caspase3和Caspase9蛋白表达量、细胞总凋亡率以及细胞迁移侵袭抑制率显著升高,顺铂组Caspase3、Caspase9蛋白表达量、细胞总凋亡率显著升高;与顺铂单用组相比,仙茅组、仙茅联用顺铂组Caspase3和Caspase9蛋白表达、细胞总凋亡率以及细胞迁移侵袭抑制率显著升高.结论:仙茅、顺铂、仙茅联用顺铂可以诱导A549细胞凋亡,与仙茅联用增强了顺铂对A549细胞凋亡的诱导作用,其作用机制与凋亡相关蛋白Caspase3、Caspase9有关.同时,联用仙茅后顺铂对A549细胞增殖率及迁移侵袭能力的抑制作用也更加显著.
Objective:To explore of the mechanism of Curculiginis Rhizoma,a traditional Chinese medicine,sensitizing lung cancer cells to cisplatin chemotherapy.Methods:Network pharmacology and molecular docking techniques were used to screen the main apoptotic proteins of Curculiginis Rhizoma in non-small cell lung cancer;CCK-8 assay was performed to measure cell pro-liferation rate;Western blot was used to detect the expression levels of cleaved Caspase3 and cleaved Caspase9 proteins in lung cancer cells(A549)after treatment with Curculiginis Rhizoma,cisplatin alone,and in combination;flow cytometry was used to detect the total apoptosis rate of cells;cell scratch and invasion experiments were conducted to assess cell migration and invasion capabilities.Results:At a concentration of 100-1 500 μg/mL,the water extract of Curculiginis Rhizoma showed no significant in-hibitory effect on the proliferation of A549 cells.However,the combined treatment showed a significantly enhanced inhibitory ef-fect on A549 cells compared to cisplatin alone.Compared to the control group,the Curculiginis Rhizoma group and the combined treatment group demonstrated significantly increased expression levels of Caspase3 and Caspase9 proteins,total apoptosis rate,as well as cell migration and invasion inhibition rate.The cisplatin group showed significantly increased expression levels of Caspase3 and Caspase9 proteins,as well as the total apoptosis rate,compared to the control group.Additionally,compared to the cisplatin alone group,the Curculiginis Rhizoma group and the combined Curculiginis Rhizoma and cisplatin group demonstrated significant-ly increased expression of Caspase3 and Caspase9 proteins,total apoptosis rate,and cell migration and invasion inhibition rate.Conclusions:Curculiginis Rhizoma,cisplatin,and the combination of Curculiginis Rhizoma with cisplatin can induce apoptosis in A549 cells.The combination with Curculiginis Rhizoma enhances the induction of apoptosis by cisplatin in A549 cells,and its mechanism is related to the apoptosis-associated proteins Caspase3 and Caspase9.Additionally,the combined treatment of Curcu-liginis Rhizoma followed by cisplatin shows a more pronounced inhibitory effect on the proliferation,migration,and invasion capa-bilities of A549 cells.
黄鑫;华国栋;王萌;刘文卉;高若瑜;程娇娇;朱宝琛;薛春苗
北京中医药大学东直门医院,北京 100700北京中医药大学中药学院,北京 102488
中医学
非小细胞肺癌仙茅顺铂细胞凋亡Caspase3Caspase9
Non-small cell lung cancerCurculiginis RhizomaCisplatinApoptosis of cellsCaspase3Caspase9
《海南医学院学报》 2024 (019)
1486-1496 / 11
This study was supported by Clinical Traditional Chinese Medicine,a high-level key discipline of the State Administration of Traditional Chinese Medicine(zyyzdxk-2023257) 国家中医药管理局高水平重点学科临床中药学(zyyzdxk-2023257)
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