卵泡刺激素受体介导的CA125靶向沉默及其与靶向化疗协同治疗卵巢癌

卵巢癌的治疗长期处于停滞不前状态，以卵巢癌发生发展的分子机制和特殊激素环境为基础，寻找有效治疗方法可能具有更好的前景。研究发现，作为卵巢癌诊断和随访标志物的癌抗原125（cancer antigen 125, CA125）是卵巢癌发生发展中的一个重要靶点，尤其是在腹腔种植转移中具有关键作用。本研究拟借助卵泡刺激素受配体的介导，在提高靶向性的基础上，制备以CA125编码基因MUC16 的siRNA为弹药，纳米材料为载体的靶向药物，将MUC16 siRNA选择性导入卵巢癌细胞，沉默MUC16表达，考察CA125在体内外环境下对卵巢癌细胞粘附、种植和转移的影响，并结合FSH受体介导的靶向化疗药物，在卵巢癌细胞种植转移受到抑制的同时杀灭肿瘤细胞。这项研究有利于人们深入理解CA125的生物学功能，而且能够通过双重靶向提高CA125拮抗策略对卵巢癌的杀伤作用，为肿瘤靶向治疗研究提供新思路。

Ovarian cancer is the leading cause of gynecologic malignancies. Most patients are diagnosed at advanced stages and have only a 30% 5-year survival rate. Recent years the survival rate of patients with ovarian cancer has not been improved significantly. It could be a promising approach to develop therapeutics based on etiology and hormone environment of ovarian cancer. Cancer antigen 125 (CA125) is commonly expressed in ovarian cancer and has been used for early detection, distinguishing malignant from benign pelvic masses, monitoring response to treatment and detecting recurrence. Recent data indicate that CA125 contributes to the pathogenesis and progression of ovarian cancer, especially in peritoneal implantation and metastasis. To specific silence the expression of CA125, our study will develop follicle-stimulating hormone receptor (FSHR)-mediated MUC16 (CA125 coding gene) siRNA nanoparticule. The cytotocity, transfection efficiency and MUC16 silencing effect will be evaluated respectively. Moreover, the impact of specific CA125 silencing on ovarian cancer cell adhesion, implantation and metastasis will be detected in vitro and in vivo. To destroy tumor cells at the same time ovarian cancer implantation and metastasis are suppressed by CA125 silencing, this novel targeted complex will be administrated to animal model of ovarian cancer combined with FSH receptor-mediated paclitaxol nanoparticles. Tumor growth, peritoneal implantation and survival of animal models will be evaluated. Our study will provide evidence for a critical role of CA125 in ovarian cancer progression, and provide a strong experimental foundation for targeted therapy against ovarian cancer.