ABSTRACT
Aim To explore the effects of anti-HER-2 chimeric antibody chA 21 on proliferation and apoptosis of SKBR3 cells.Methods MTT colorometric assay,HE staining,transmission electron microscopy,flow cytometry,and TUNEL were used to study the proliferation inhibition and apoptosis induction of SKBR3 cells by chA 21 in vitro.Results Proliferative inhibition rates and apoptotic index of SKBR3 cells were increased in a dose and time dependent manner after exposure to chA21(0.2～5.4 mg?L~(-1)).Conclusion chA 21 could remarkably inhibit proliferation of SKBR3 cells in vitro and apoptosis induction may be one of its main mechanisms.
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.
ABSTRACT
Objective To investigate the effect of an anti-HER-2 engineered antibody,chA21,on the expression of MMP-2 and TIMP-2 in human ovarian cancer SKOV3 cells that highly express HER-2.Methods After exposure to chA21 at concentrations of 6 mg/L and 12 mg/L for 36 hours,respectively,the expression of MMP-2 and TIMP-2 proteins was detected by immunocyctochemistry.SKOV3 cells were inoculated into nude mice to establish animal models.The mice were respectively administered with normal saline and chA21(30 mg/kg) via injection twice a week for 6 consecutive weeks,and then were killed after 44 days' administration of the drugs.Immnohistochemical staining of MMP-2 and TIMP-2 was observed on tissue microarray sections.Results After exposed to chA21,TIMP-2 protein was increased(P
ABSTRACT
Objective To study the anti-tumor effect of anti-HER-2 engineering antibodies chA21 and Herceptin on nude mice xenografts of human ovarian cancer SKOV3 cells and explore its mechanism.Methods An animal model with human ovarian cancer SKOV3 cells involved in nude mice was established and the mice were randomized into 3 groups: normal saline(NS),chA21 and Herceptin.The mice were respectively administrated with Herceptin(30mg/kg) and chA21(30mg/kg) via caudal vein injection twice a week for consecutive 6 weeks,and then were killed after 44 days adminstration of the drugs.The volumes of the xenografts were measured twice a week.The tumor weight and inhibition ratio were measured after mice were killed.Ki67 and NF?B expression in the three groups was quantificationally analyzed by immunohistochemistry on tissue microarray sections combined with a micro-image analysing system.Results The growth of xenografts of human ovarian cancer SKOV3 cells in nude mice was significantly inhibited by either Herceptin or chA21. Both Ki-67 labeling indices and NF?B levels in chA21 and Herceptin groups were lower than those in the control(P