DNA methylation profile of adipocytes treated with DNMT inhibitor, guadecitabine (100nM, 3X daily).

Ovarian cancer (OC) cells frequently metastasize to the omentum and adipocytes play a significant role in ovarian tumor progression. Therapeutic interventions targeting aberrant DNA methylation in ovarian tumors have shown promise in the clinic but the effects of epigenetic therapy on the tumor microenvironment are understudied. Here, we examined the effect of adipocytes on OC cell behavior in culture and impact of targeting DNA methylation in adipocytes on OC metastasis. The presence of adipocytes increased OC cell migration and invasion and proximal and direct co-culture of adipocytes . Treatment of adipocytes with hypomethylating agent guadecitabine decreased migration and invasion of OC cells towards adipocytes.

卵巢癌（Ovarian Cancer, OC）细胞常向网膜发生转移，脂肪细胞在卵巢肿瘤进展中发挥关键调控作用。以卵巢肿瘤异常DNA甲基化为靶点的治疗干预策略已在临床展现出应用潜力，但表观遗传治疗对肿瘤微环境的影响仍未得到充分研究。本研究探究了体外培养体系中脂肪细胞对OC细胞行为的影响，以及靶向脂肪细胞DNA甲基化的干预手段对OC转移的作用。实验结果表明，脂肪细胞的存在可增强OC细胞的迁移与侵袭能力，该效应可通过与脂肪细胞进行近距离直接共培养得以证实。使用低甲基化剂呱地他滨（guadecitabine）处理脂肪细胞，可显著降低OC细胞向脂肪细胞迁移及侵袭的能力。