Enhanced sensitization to paclitaxel-induced apoptotic effect on breast cancer cells SKBr3 by engineered antibody treatment / 中国免疫学杂志

ABSTRACT

Objective:To explore the enhanced sensitization to chemotherapeutic agent paclitaxel-induced apoptotic effect on p185-overexpressing human malignant breast cancer cell lines SKBr3 by anti-p185c-erbB-2/neu engineered antibody treatment and to study its emerging mechanism.Methods:The proliferative inhibitory effect was assessed by MTS assay; Cells stained with AnnexinV-FITC and PI were used to qualify the apoptotic cell number by FACS(Fluorescence-activated cell sorting) analysis; Phosphorylation of Ser473 AKt and p65 NF-?B subunit were determined by Western blot; NF-?B-DNA binding activity was demonstrated by EMSA(Electrophoretic mobility shift assay).Results:Anti-p185c-erbB-2/neu engineered antibody rendered SKBr3 cells more susceptible to paclitaxel-induced proliferative inhibition, which further attributed to apoptotic induction; Furthermore, combination of the engineered antibody and paclitaxel also showed effective suppression of AKt/NF-?B pathway in SKBr3 cells.Conclusion:The aggressiveness of AKt/NF-?B pathway was partly attributed to its resistance to paclitaxel-induced apoptosis. Anti-p185c-erbB-2/neu engineered antibody plus paclitaxel combination rendered p185-overexpressing human malignant breast cancer cells SKBr3 more susceptible to paclitaxel-induced apoptosis by efficient suppression of AKt/NF-?B pathway.