肿瘤干细胞具有自我更新和分化潜能，对外界理化因子的杀伤作用不敏感，被认为是肿瘤复发的原因之一，但其机制尚不明确。近来，研究报道肿瘤干细胞自我更新能力受铁调控，且对铁死亡的敏感性高于非干细胞。本项目前期定量蛋白质组学结果显示，NSDHL在3AO卵巢癌干细胞的表达高于非干细胞，并经不同细胞系验证。下调NSDHL促进卵巢癌干细胞死亡，加入铁死亡抑制剂逆转该现象，初步证实NSDHL参与卵巢癌干细胞铁死亡的调控。随后我们发现铁稳态调节因子LXRα的表达随NSDHL下调而降低。本项目拟在已有工作基础上采用无血清悬浮培养、基因调控等手段观察调控NSDHL对卵巢癌干细胞铁死亡的影响，并通过共转染、抑制剂等技术证实LXRα参与NSDHL对铁死亡的调控，最后通过动物实验及临床组织标本验证该机制。阐明NSDHL调控卵巢癌干细胞铁死亡的崭新机制，为肿瘤干细胞靶向研究提供新的方向，为卵巢癌治疗提供新的科学证据。

Cancer stem cells (CSCs) possess the ability of self-renewal, differentiation potential，and non-sensitivity to physical and chemical factors, which is regarded as a cause of cancer recurrence, but the mechanism is currently unclear. Lately, some research reported that the ability of self-renewal of CSCs was regulated by iron, and CSCs were more sensitivity than non-stem cells. On the basis of our previous study by LC-MS/MS-based label free quantitative proteomics，the expression of NSDHL was significantly higher in ovarian cancer stem cells than parent cells , following qPCR and western blotting validation. Then we showed that a promotion of death in cancer stem cells by NSDHL knock-down, which was reversed with a ferroptosis inhibitor. We verified that NSDHL may participate in the regulation of ferroptosis in ovarian cancer stem cells. However, the mechanism is still unknown. Following we confirmed that the iron balance regulator, LXRα, was decreased along with NSDHL knock-down. In this study proposal, we plan to observe the impact on ferroptosis of ovarian cancer by regulating NSDHL expression through serum-free culture and gene modulation. To identify that LXRα may participate in the process of NSDHL mediating the ferroptosis regulation in ovarian cancer stem cells using co-transfection and inhibitor. Finally, To verify the relationship between NSDHL and LXRα in clinical ovarian cancer tissue samples and animal models. Classifying the novel mechanism of NSDHL in ferroptosis of ovarian cancer stem cells will enrich the theory of ovarian cancer stem cells, provide a new thinking for developing anti-tumor drug and find out a potential strategy for ovarian cancer therapy.