目前文献报道和本课题组前期发现外泌体可以通过外排顺铂增加卵巢癌细胞对顺铂的耐受性，但是外泌体释放的调控机制目前尚不清楚。我们前期研究发现下调O-GlcNAc转移酶（OGT）能增加卵巢癌细胞的顺铂耐药性，进一步研究发现OGT作为糖基化修饰转移酶能调控SNAP-23的翻译后修饰，同时研究发现 SNAP-23参与调控卵巢癌细胞外泌体的释放。因此我们推测SNAP-23的O-GlcNAcylation修饰参与调控卵巢癌细胞的外泌体释放，通过控制外泌体的释放量影响细胞内顺铂外排产生耐药。本研究拟从外泌体转运顺铂以及其与耐药的关系、下调OGT对外泌体释放的影响以及SNAP-23的O-GlcNAcylation修饰调控外泌体释放的分子机制三个方面探讨O-GlcNAcylation修饰介导的外泌体释放参与卵巢癌细胞耐药形成的相关机制，为卵巢癌耐药的临床治疗应用提供理论依据。

Previous studies and our research group have found that exosomes can increase cisplatin tolerance of ovarian cancer cells by efflux of cisplatin, but the regulatory mechanism of exosome release remains unclear. Our previous study found that down-regulation of o-glcnac transferase (OGT) could increase the cisplatin resistance of ovarian cancer cells. Further study found that OGT, as a glycosylated transferase, regulated the post-translational modification of SNAP-23, and that SNAP-23 was involved in the regulation of exosome release in ovarian cancer cells. Therefore, we speculated that O-GlcNAcylation of SNAP-23 was involved in the regulation of exosome release in ovarian cancer cells, and the regulation of exosome release could affect the intracellular cisplatin efflux. This project will conduct three parts of experimental works to explore mechanism of O-GlcNAcylation modified mediated exosome release involved in ovarian cancer cells resistant mechanism, including exosome efflux cisplatin and its relationship with the resistance, the effect of downregulation of OGT on exosome release and the molecular mechanism of regulation of exosome release by O-GlcNAcylation modification of SNAP-23. This study provides a theoretical and experimental basis for the clinical treatment of ovarian cancer drug resistance.