Inhibiting L1CAM Reverses Cisplatin Resistance of Triple Negative Breast Cancer Cells by Blocking AKT Signaling Pathway

Abstract

DDP-resistant MDA-MB-231 cells (MDA-MB-231/DDP) cells had higher expression of L1CAM than their parental cells. L1CAM siRNA decreased the IC50 of MDA-MB-231/DDP cells to DDP. L1CAM inhibition down-regulated p-AKT/AKT in MDA-MB-231/DDP cells; meanwhile, it could promote MDA-MB-231/DDP cell apoptosis, inhibit cell EMT, invasion, and migration. Moreover, SC79 (an AKT activator) increased the DDP-resistance of MDA-MB-231/DDP cells, which was reversed by L1CAM inhibition. Furthermore, co-treatment of L1CAM shRNA and cisplatin injection had better anti-tumor effects in vivo than these two single treatments with decreased p-AKT/AKT. Thus, silencing L1CAM reversed the DDP resistance by inhibiting the AKT pathway.

Keywords:

• Triple negative breast cancer
• L1CAM
• cisplatin
• drug resistance
• AKT

Declaration of interest

No potential conflicts of interest were disclosed.

Data availability statement

All relevant data are within the paper.