Anti-tumor Effect Of Trastuzumab On Nude Mice Xenografts Of Human Ovarian Cancer SKOV3 Cells And Its Synergistic Effect Of Action With Docetaxel, Cisplatin

Objective 1. To study the anti-tumor effect of anti-HER-2 humanized monoclonal antibodies Trastuzumab on nude mice xenografts of HER-2-overexpressing human ovarian cancer SKOV3 cells,explore its possible mechanism and compare the anti-tumor effect with ovarian cancer first-line chemotherapy drugs cisplatin,docetaxel;2.To compare the anti-tumor effect of Trastuzumab with the combination of DDP or(and) docetaxel with ovarian cancer first-line chemotherapy regimens (TP scheme) on nude mice xenografts of human ovarian cancer SKOV3 cells.Methods An animal model with human ovarian cancer SKOV3 cells involved in nude mice was established and the mice were randomized into 8 groups:①Herceptin group,②Taxotere group,③DDP group,④Herceptin plus Taxotere group,⑤Herceptin plus DDP group,⑥Taxotere plus DDP group,⑦Herceptin plus Taxotere plus DDP group,⑧NS group,There are 4 mice in every group. The mice were administrated respectively with Herceptin (20mg/kg),Taxoter(e5mg/kg),Cisplatin(3mg/kg) via caudal vein injection once a week for consecutive six weeks. The size of the tumor and mice weight were measured weekly, then the mice were killed a week after last treatment. The inhibition ratio of tumor growth was calculated and tumor tissues were observed by using HE staining. The apoptotic index was analyzed by using Tunel technique. The Ki-67 expression in xenograft tumors were analyzed by using immunohistochemical staining.Results 1. Contrast to control group,Herceptin can obviously inhibit the growth of xenografts of human ovarian cancer SKOV3 cells in nude mice, which is statistically significant (P<0.05),while compared to Taxotere group and DDP group, it is statistically insignificant (P>0.05);Contrast to every single drug group, Herceptin plus Taxotere group,Herceptin plus DDP group can more obviously inhibit the growth of tumor, which is statistically significant (P<0.05),while each compared to TP scheme, it is statistically insignificant (P>0.05);Contrast to every other group, Herceptin plus Taxotere plus DDP group has the most obviously inhibition to the growth of tumor, which is statistically significant(P<0.05);2. Detected by TUNEL: Contrast to control group,the tumor cell apoptotic index of Herceptin group was significantly increased, which is statistically significant (P<0.05),while compared to Taxotere group and DDP group, it is statistically insignificant(P>0.05); Contrast to every single drug group,the tumor cell apoptotic index of Herceptin plus Taxotere group,Herceptin plus DDP group are higher, which is statistically significant(P<0.05),while each compared to TP scheme, it is statistically insignificant (P>0.05);Contrast to every other group, the tumor cell apoptotic index of Herceptin plus Taxotere plus DDP group is the highest, which is statistically significant(P<0.05);3. Detected by ICH: Contrast to control group, the Ki-67 expression ratio in xenograft tumors of Herceptin group was significantly reduced, which is statistically significant(P<0.05),while compared to Taxotere group and DDP group, it is statistically insignificant (P>0.05); Contrast to every single drug group,the Ki-67 expression ratio in xenograft tumors of Herceptin plus Taxotere group,Herceptin plus DDP group are lower, which is statistically significant(P<0.05),while each compared to TP scheme, it is statistically insignificant (P>0.05);Contrast to every other group, the Ki-67 expression ratio in xenograft tumors of Herceptin plus Taxotere plus DDP group is the lowest, which is statistically significant(P<0.05);Conclusion 1. Herceptin can effectively inhibit the growth of xenografts of human ovarian cancer SKOV3 cells in nude mice, and can produce equivalent tumor inhibition with ovarian cancer first-line chemotherapy drugs Taxotere and DDP,down-regulation of Ki-67 expression in SKOV3 cells,and induction of tumor cell apoptosis might be one of its possible mechanisms;2.There are synergistic mechanism between Herceptin and Taxotere,DDP, they can more effectively inhibit the growth of tumor,moreover, Herceptin plus Taxotere,Herceptin plus DDP can produce equivalent tumor inhibition with TP scheme;3. Herceptin,Taxotere,DDP three drugs'combination can produce the most effectively inhibition to the growth of tumor, Herceptin can further enhance the TP scheme to the growth of tumor.