溶瘤型腺病毒介导的抗CD44单克隆抗体对CD44+CD117+卵巢癌细胞的作用及其机制探讨

The key of the targeted therapy for ovarian stem cells is the choice of targets.Studies have shown that CD44 is one of the important surface markers in epithelial ovarian cancer stem cells ,however whether CD44 could become the target for targeted therapy of ovarian stem cells is unclear. In our previous research, we have proved that:anti-CD44 monoclonal antibody could change the cell cycle of the CD44 positive epithelial ovarian cancer cells, promote their apoptosis, reduce their motile and invasion ability, and enhance their sensitivity to drugs. So in this research,to verify CD44 could become the target for targeted therapy of ovarian stem cells, we will further discuss the effect of anti-CD44 monoclonal antibody on CD44+CD117+ovarian cancer cells. Further more ,we will discuss the mechanism from gene level and protein level by Co-immunoprecipitation,two-dimensional protein electrophoresis. Then we will build a selective replication adenovirus expressing anti-CD44 monoclonal antibody, then the expression ability of the recombined adenovirus and the antibody activity will be detected, and the therapy effect of the recombined adenovirus will be verified in vivo and in vitro. Thus opening a new, effective treatment method for the treatment of the epithelial ovarian cancer.

卵巢癌干细胞的靶向治疗的关键在于靶点的选择，CD44是上皮性卵巢癌干细胞表面标志分子之一，但其能否成为卵巢癌干细胞的靶向治疗的靶点尚不明确。在我们前期的研究工作显示：抗CD44单克隆抗体能改变CD44阳性的上皮性卵巢癌细胞的细胞周期，促进其凋亡，降低其运动侵袭能力，并增强其对化疗药物的敏感性，因此，在本项目中，我们将进一步探讨抗CD44单克隆抗体在体内外对CD44+CD117+卵巢癌细胞的作用，从而明确CD44能否成为卵巢癌干细胞靶向治疗的靶点，进一步采用二维蛋白电泳、质谱分析结合基因芯片等技术分别从蛋白以及基因水平探讨其作用机制，并以此为切入靶点，构建表达抗CD44单克隆抗体的溶瘤型腺病毒，检测该重组腺病毒在体内外对抗CD44单克隆抗体表达的滴度及活性；并探讨其在体内外对CD44+CD117+卵巢癌细胞的治疗作用，从而为上皮性卵巢癌的治疗提供一个全新的、有效地治疗方式。