中文摘要
化疗耐药是卵巢癌预后差的主要原因,microRNA在铂类耐药为主的卵巢癌耐药性研究结果多基于细胞学的研究及肿瘤样本的芯片筛选,但耐药靶基因调控网络之间的关系还尚未明了。自噬与肿瘤的发生发展密切相关,但到目前为止其与肿瘤耐药性的文章仅有2篇。我们通过前期研究筛选出化疗耐药和化疗敏感卵巢癌之间差异表达明显的miRNA-141,预测PTEN是其最有可能潜在靶基因,且我们发现PTEN/AKT/NF-κB 能参与到自噬作用中,本项目拟通过构建miRNA逆转录病毒表达载体和其反义寡核苷酸,采用生物化学、免疫学及分子生物学等研究方法,证明miRNA-141能通过靶基因PTEN,通过NF-κB信号通路参与自噬,并探讨自噬与卵巢癌耐药的关系,从一个全新的角度阐明卵巢癌耐药发生的分子机制,为卵巢癌治疗提供新的思路,最终提高患者五年生存率。
英文摘要
Chemosensitize drug resistant is the world's leading cause of death in ovarian cancer。The findings of platinum resistance of miRNA in oophoroma is only cytology and chip screening,but target gene regulation of resistnce doesn't clear .Autophagy play important roles in the initiation and progression of malignancies.Drug-resistance of the mechanisms of it is only two articles.We find miRNA141 by robust selection procedures in chemotherapy-resistance and chemotherapy-sensitive carcinoma of ovary and pretest PTEN thzt is likely to target gene.We also detect that PTEN/AKT/NF-κB should participate in autophapy.Our project will set up retroviral vector and antisense oligonucleotide of miRNA141 and adopt the research method of biochemistry、immunology and molecular biology to prove miRNA141 could participate autophagy by target gene PTEN and NF-κB signal pathway and to discuss the connection of autophagy and resistance.We clarificate molecule mechanism of resistance of ovarian cancer from a new standpoint and provide a new method to therapy of ovarian cancer to improve 5-Year Survival Rates .
