摘要
目的 探讨川楝素(TSN)联合奥拉帕尼在三阴性乳腺癌(TNBC)中的作用机制。方法 体外培养人TNBC细胞系MDA-MB-231,利用0.1μmol/L TSN和0.5、1.0、5.0μmol/L奥拉帕尼单独或共同处理,评估TSN联合奥拉帕尼对MDA-MB-231自噬水平及细胞活力的影响。选取4例TNBC患者的新辅助化疗后肿瘤残留手术标本,建立患者来源类器官(PDOs)模型,分为5μmol/L、10μmol/L奥拉帕尼组,0.05μmol/L TSN组和TSN+奥拉帕尼组(0.1μmol/L TSN分别与5、10μmol/L奥拉帕尼联合处理)。检测TSN联合奥拉帕尼在TNBC患者中的药物敏感性,验证TSN联合奥拉帕尼是否能够在PDOs模型中发挥肿瘤杀伤作用。结果 奥拉帕尼在MDA-MB-231细胞系中诱导自噬,相比单独使用奥拉帕尼,TSN和5.0μmol/L奥拉帕尼联合使用可抑制MDA-MB-231细胞的增殖(P<0.01)。在TNBC的PDOs模型中,与单用奥拉帕尼相比,加用TSN后细胞死亡率明显升高(P<0.01)。结论 TSN联合奥拉帕尼的肿瘤杀伤作用优于单独使用奥拉帕尼,其机制可能与抑制自噬有关。
Objective To investigate the anti-tumor mechanism of natural compound toosendanin(TSN)combined with olaparib in triple-negative breast cancer(TNBC).Methods Human TNBC cell line MDA-MB-231 was cultured in vitro.Effects of TSN combined with olaparib on autophagy levels and cell viability in MDA-MB-231 cells were evaluated using 0.5,1.0,and 5.0μmol/L olaparib alone or in combination.Surgical specimens from four TNBC patients who had residual tumors after neoadjuvant chemotherapy were selected to establish patient-derived organoid(PDO)models.The drug sensitivity of TSN combined with olaparib in TNBC patients was detected.Whether TSN combined with olaparib can exert autophagy inhibitory effects and tumor-killing effects in organoid model was verified.Results Olaparib induced autophagy in MDA-MB-231 cell line,and the combination of TSN and olaparib inhibited the proliferation of MDA-MB-231 cells(P<0.01).In the TNBC PDOs model,the therapeutic effect of olaparib combined with TSN can significantly reduce the proliferation ability of tumor cells compared with olaparib alone.Conclusion The tumor-killing effect of TSN combined with olaparib is superior to that of olaparib alone,and the mechanism may be related to autophagy inhibition.
作者
黄慧琦
伍秋苑
张昆
李佩贤
熊亚明
叶国麟
周丹
HUANG Huiqi;WU Qiuyuan;ZHANG Kun;LI Peixian;XIONG Yaming;YE Guolin;ZHOU Dan(Department of Breast Surgery,Foshan First People's Hospital,Foshan 528000,China;the First School of Clinical Medicine,Guangdong Medical University;Foshan First People's Hospital Translational Medicine Research Institute)
出处
《天津医药》
2025年第9期897-903,共7页
Tianjin Medical Journal
基金
广东省中医药局科研课题(20231324)
广东省基础与应用基础研究基金(2022A1515140091)
佛山市登峰计划项目(2020B18)
广东省医学科学技术研究基金(A2019329)。
关键词
三阴性乳腺癌
川楝素
自噬
类器官
抗肿瘤药
植物
奥拉帕尼
协同作用
triple negative breast neoplasms
toosendanin
autophagy
organoids
antineoplastic agents,phytogenic
olaparib
synergistic effect
