摘要
[Objectives]To investigate whether Ailanthone(AIL)could reverse cisplatin resistance in non-small cell lung cancer(NSCLC)by modulating autophagy pathways in A549/DDP cells.[Methods]Cisplatin-resistant A549/DDP cells were treated with AIL(0.6μmol/L),cisplatin(50μg/mL),or their combination.Cell proliferation was assessed by MTT,EdU and colony formation assays;migration by Transwell and wound healing assays;autophagy markers(P62,LC3B,Beclin1,ATG5)by Western blot;LC3B puncta by immunofluorescence;with rescue experiments using rapamycin.[Results]The AIL-cisplatin combination synergistically inhibited proliferation and migration,while downregulating P-gp and MVP.AIL significantly increased P62 accumulation while decreasing LC3B-II,Beclin1 and ATG5.Rapamycin reversed these effects,restoring viability and resistance markers.[Conclusions]AIL reverses cisplatin resistance in NSCLC by inhibiting autophagy through P62/LC3B regulation,offering a promising therapeutic strategy for refractory NSCLC.
基金
Supported by National Natural Science Foundation of China(81703001)
Key R&D Project of Hebei Province(19277783D)
Natural Science Foundation of Hebei Province(H2021406021)
Chengde Medical University Discipline Construction Funds.