DOI: 10.11958/20250238
Research on the anti-tumor mechanism of toosendanin combined with olaparib in triple negative breast cancer
HUANG Huiqi
WU Qiuyuan
ZHANG Kun
LI Peixian
XIONG Yaming
YE Guolin
ZHOU Dan
Abstract：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 5.0 μmol/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.
Keywords：triple negative breast neoplasmstoosendaninautophagyorganoidsantineoplastic agentsphytogenicolaparibsynergistic effect
Publication Date：2025-09-15
Online Publishing Date：2025-09-23(First online date of this platform, not the publication date of the document)
Pages：7( 897-903 )