Effect and mechanism of FOXP1 on the viability and apoptosis of cisplatin resistant cervical cancer cells

WANG Xiao; DONG Qianjing

doi:10.12173/j.issn.1004-5511.202411179

Abstract：Objective To investigate the effect and underlying mechanism of fork-head box protein 1(FOXP1)on the viability and apoptosis of cisplatin(DDP)resistant cervical cancer cells.Methods Construction of FOXP1 interference DDP-resistant cervical cancer cell models using siRNA.Cell viability was assessed using CCK-8 assay,apoptosis was measured by flow cytometry,autophagy levels were detected via LC3 immunofluorescence,and changes in autophagy-related proteins and Wnt/β-catenin signaling pathway components were analyzed by Western blot.Functional rescue experiments were performed using the autophagy activator rapamycin(RAPA)or the Wnt pathway activator SKL2001 in FOXP1-silenced HeLa/DDP cells.Results Compared to normal cervical cancer cells,FOXP1 was highly expressed in DDP-resistant HeLa/DDP and SiHa/DDP cells.Inhibition of FOXP1 significantly reduced the cellular activity of HeLa/DDP and SiHa/DDP,elevated the sensitivity of cells to DDP,and promoted apoptosis.Additionally,FOXP1 silencing downregulated LC3-Ⅱ and Beclin-1 protein expression while upregulating LC3-I and p62,indicating suppressed autophagy and Wnt/(3-catenin signaling activation.These effects were partially reversed by RAPA or SKL2001 treatment.Conclusion FOXP1 can elevate autophagy to reduce the sensitivity of cervical cancer DDP-resistant cell lines HeLa/DDP and SiHa/DDP to DDP by activating the Wnt/β-catenin signalling pathway.