Study on ICAM1 Influencing the Function of Drug-resistant Cells in Triple-negative Breast Cancer

YANG Hongdao; TAO Wei

doi:10.3969/j.issn.2096-305X.2025.06.004

Abstract：Objective To investigate the changes in cellular functions by which the ICAM1 gene regulates chemotherapeutic resistance to doxorubicin/paclitaxel in triple-negative breast cancer(TNBC).Methods TNBC samples without preoperative neoadjuvant chemotherapy and those with preoperative neoadjuvant chemotherapy were collected.Immunohistochemistry(IHC)and Western Blot(WB)were used to detect ICAM1 expression.qRT-PCR and WB were applied to detect ICAM1 expression in breast cancer cells.Chemoresistant cell lines were established by treating TNBC cells with combined doxorubicin and paclitaxel.Lentivirus vectors for human ICAM1 knockdown were constructed and infected into resistant cells.Cell proliferation was evaluated by CCK-8 and Edu assays.Cell migration and invasion were detected by Transwell assays.Western Blot was performed to detect the expression of ferroptosis-related proteins(GPX4,ACSIA,SLC7A11),breast cancer resistance protein ABCG2,and EMT-related proteins(E-cadherin,N-cadherin,Vimentin).Cellular ATP levels were measured using an ATP kit,and lipid peroxidation levels were detected by DCHF-DA probe.Results Lentivirus-mediated ICAM1 knockdown in MDA-MB-231 sensitive and resistant cell lines showed that ICAM1 promoted cell viability,proliferation,migration,and invasion;enhanced the expression of breast cancer resistance protein ABCG2;inhibited ferroptosis;and promoted the EMT process.Conclusion This study reveals that ICAM1 promotes the proliferation and invasion of breast cancer cells by regulating cellular metabolism,EMT process,and ferroptosis pathway.Meanwhile,ICAM1 contributes to chemoresistance by upregulating the expression of breast cancer resistance protein ABCG2.