Anti-tumor Effect Of Anti-HER-2 Engineered Antibodies ChA21 On Nude Mice Xenografts Of Human Ovarian Cancer SKOV3 Cells And Exploration Of Its Mechanism

Objective To study the anti-tumor effect of anti-HER-2 engineered antibodies chA21 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: 12 in normal saline group (negative control), 6 in chA21 group and 6 in Herceptin (positive control). The mice were administrated respectively with chA21 (30mg·kg^-1) and Herceptin (30mg·kg^-1) via caudal vein injection twice a week for consecutive 6 weeks, and then were killed after 44 day's administration 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. Pathological changes of tumor tissues were observed. AB/PAS staining was used to evaluate the mucus production. HE staining, electron microscopy and TIJNEL staining were used to detect the apoptosis induction by chA21 in SKOV3 cells. Expression of Ki-67, NFκB, Bax, Bcl-2, caspase 3, Fas, MMP-2, MMP-9, MMP1, TIMP-2, VEGF and E-cad in the three groups was quantificationally analyzed by immunohistochemistry (S-P method) on tissue microarray sections combined with a micro-image analyse system. Results 1) The growth of xenografts of human ovarian cancer SKOV3 cells in nude mice was significantly inhibited by chA21 with 30.53% of the tumor inhibitory ratio. 2) Both Ki-67 labeling index and NFkB protein expression in chA21 group were lower than those in the negative control. 3) A tendency of tumor cell nests and glandular formation in chA21 group was observed by...