晚期卵巢癌患者在治疗后大多复发或耐药使治疗失败，死亡率居高不下。研究表明随卵巢表面上皮细胞向恶性的逐步转化，细胞代谢逐渐向糖酵解方式转变。癌细胞对能量代谢的这种重编程保证了其快速增殖和抵抗杀伤所需能量和物质，如能对其进行转变有可能改善疗效。如何选择性在卵巢癌病灶阻断糖酵解途径，使癌细胞能量代谢向正常方式转变，从而阻止细胞对药物的抵抗，值得深入探索。我们前期工作表明，在载体上修饰以可与卵巢癌细胞表面卵泡刺激素受体结合的配体有助于提高药物靶向分布。本项目拟构建卵泡刺激素受体介导的靶向卵巢癌糖酵解关键酶的复合治疗系统，通过主动和被动靶向，有效沉默其在卵巢癌的表达，使癌细胞不能获取足够支持，难以对化疗药产生适应性保护而被杀灭；并研究卵巢癌能量代谢方式转变后，细胞恶性生物学行为和化疗耐药性的改变及机制。本研究对阐明卵巢癌异常能量代谢有重要意义，并为靶向治疗临床应用奠定基础，为化疗增敏研究提供新思路。

Ovarian cancer is the leading cause of gynecologic malignancies. Most patients are diagnosed at advanced stages and have only a 30% five-year survival rate. Those patients at advanced disease stage will often recur and develop chemoresistance. The metabolic changes in distinct disease stages have been studied using ovarian surface epithelial cancer progression model. The cell metabolism is shifted to a more glycolytic phenotype as ovarian cancer progresses. The dependency on aerobic glycolysis of cancer cells is necessary to sustain their growth and proliferation. Moreover, the drug-induced apoptosis is decreased because of the increased energy production and metabolite synthesis. The shifting in metabolic pathways is linked to therapeutic resistance. Therefore, the alteration of cancer metabolism could be an effective strategy for cancer treatment. It is worth to study how selectively blocking the glycolytic pathway in ovarian cancer cells but not other normal cells. The ovary is the main target organ of follicle-stimulating hormone (FSH), which binds to its receptor with high affinity. The expression of FSH receptor (FSHR) is limited in the reproductive system and has also been found in ovarian cancer. Our previous work has shown that the drugs are selectively delivered into ovarian cancer cells because of the modification with FSH peptides on the surface of drug carriers. This project will develop FSH peptide-modified nanoparticle loading siRNA of glycolytic key enzymes to specific silence their expression in ovarian cancer by active and passive targeting. The decreasing of glycolysis will promote drug-induced apoptosis of ovarian cancer cells. Thus, the targeted nanoparticle complex of suppressing glycolysis could enhance therapeutic efficacy and overcome chemoresistance of ovarian cancer. Additionally, the impacts and mechanisms of silencing glycolytic key enzymes on malignant biological behaviors and chemoresistance of ovarian cancer will be studied in vitro and in vivo. This study will provide clues for the research on abnormal energy metabolism and chemo-sensitization in ovarian cancer, and will lay the foundation for the clinical application of targeted therapy.