Ubiquitin B在逆转卵巢癌化疗耐药中的作用及机制研究

Ovarian cancer is one of the three lethal gynecological cancers.more than 60 percent of ovarian cancer patients were recurrencing in two years,and the chemotherapy resistance is the most unresolved problem in the recurrent patients.The research of cancer stem cell provided the new chance to chemotherapy resistance of ovarian cancer in recent years.However,because of lacking systematical research of chemotherapy resistance caused by ovarian cancer stem cells,this project will focus on function-effect molecullar ubiquitin B Screening from SMART library ,adopt LCM and advanced SMART library isolation technique, and systematically demonstrate the relation between ovarian cancer chemotherapy resistance and ovarian cancer stem cell characteristics regulated by ubiquitin B.Based on the previous characteristics of cancer stem cell, the project will break through the style of single chemotherapy resistant gene.From abnormal degradation of protein regulated by ubiquitin-proteasome system view, the project will explore novel method to treat andvanced stage ovarian cancer,and present the practical significance to control recurrence and improve the survival rate of ovarian cancer patients.

卵巢癌是女性生殖系统三大恶性肿瘤之一，60％以上的晚期卵巢癌患者在治疗后的2年内复发，而且复发患者因为化疗耐药使得治疗面临窘境。近年来肿瘤干细胞研究为解决卵巢癌的化疗耐药治疗难题提供了契机。由于对于卵巢癌干细胞引起的化疗耐药机制缺乏系统性研究，因此，本项目以全新的思路，从本研究组所建立的SMART 文库筛选得到的功能效应分子Ubiquitin B入手，采用SMART文库肿瘤干细胞分离技术，激光扫描流式细胞仪定量分析，动物活体成像以及蛋白组学分析，系统阐述Ubiquitin B调控下卵巢癌干细胞特性的获得与卵巢癌化疗耐药的相互关系。本项目在既往研究肿瘤干细胞特性的基础上突破了单一耐药基因研究模式，以泛素-蛋白酶体系统调控多靶点蛋白异常降解机制的视角，为卵巢癌的化疗耐药研究开辟一条新的探索途径，对控制复发，提高中晚期卵巢癌患者的生存率具有重要的现实意义和实用价值。

项目研究Ubiquitin B导致细胞内泛素-蛋白酶体系统会发生变化，导致卵巢癌细胞恶性表型发生改变，干细胞样细胞亚群比例增加，体内实验证明干扰Ubiquitin B的细胞群明显的具有干细胞的特性，在体内成瘤能力增强，对化疗药物耐药等生物学效应，蛋白组学发现了Ubiquitin B调控的作用靶点UQCRC2，综上所述，该研究对干扰Ubiquitin B的细胞群明显的具有干细胞的特性与细胞化疗耐药相互关系提供充分实验数据，为逆转化疗耐药提供了可供选择的作用靶点。项目发表SCI论文7篇，其中影响因子大于5的论文1篇，国内核心期刊论文2篇，培养博士和硕士研究生各2名。2014年作为参与人获得湖北省科技进步一等奖。