川楝素联合奥拉帕尼在三阴性乳腺癌中的抗肿瘤机制研究

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中图分类号：R737.9 文献标志码：A DOI：10.11958/20250238

Abstract：ObjectiveTo investigate the anti-tumor mechanism of natural compound toosendanin （TSN） combined with olaparib in triple-negative breast cancer （TNBC）.MethodsHuman TNBCcelline MDA-MB-231 was cultured in vitro.EffectsofTSNcombined witholaparibonautophagy levelsandcellviabilityin MDA-MB-231cellswereevaluated 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 sensitivityofTSNcombinedwitholaparib in TNBC patients wasdetected.WhetherTSNcombined witholaparibcan exert autophagy inhibitory effcts and tumor-killng effcts inorganoid model was verified.ResultsOlaparib inducedautophagy in MDA-MB-231celline，and thecombinationofTSNandolaparib inhibited the proliferationofMDA-MB-231cells（ P< 0.01）.IntheTNBCPDOsmodel，thetherapeuticefectofolaparibcombinedwithTSNcansignificantlyreduce the proliferationabilityof tumorcellscomparedwitholaparib alone.ConclusionThe tumor-kiling effectof TSNcombined with olaparib is superior to thatof olaparib alone，and the mechanism maybe related to autophagy inhibition.

Key words： triple negative breast noplasms; toosendanin;autophagy;organoids;antineoplasticagents，phytogenic; olaparib;synergistic effect

三阴性乳腺癌（triple-negativebreastcancer，TNBC）属于乳腺癌中恶性程度较高的一种亚型，无法从内分泌治疗或靶向治疗中获益，并具有侵袭性强、预后差、早期复发风险高的特点[1]。（剩余14213字）