OI inhibits development of ovarian cancer by blocking crosstalk between cancer cells and macrophages via HIF-1α pathway

Intraperitoneal implantation of ovarian cancer (OC) decreases the survival rate in clinical practice. However, there are still great deficiencies in the therapeutic strategies of inhibiting the metastasis of OC. Here, we showed that 4-octyl itaconate (OI, a cell-permeable itaconate derivative) treatment didn't influence the development of OC in vitro. Instead, OI treatment repressed the activation of peritoneal macrophages and downregulated the expression of proinflammatory factors in mice bearing OC. Besides, OI inhibited the angiogenesis of OC tissues by downregulating HIF-1α of OC that was induced by proinflammatory factors from activated macrophages. In conclusion, our findings demonstrate that OI suppresses metastasis of ovarian cancer by blocking crosstalk between cancer cells and macrophages via HIF-1α pathway, providing a potential therapeutic strategy for metastasis of OC. • OI treatment blocks crosstalk between cancer cells and macrophages during metastasis of ovarian cancer. • OI treatment represses HIF-1α pathway of ovarian cancer cells. • OI is identified as a potential therapeutic agent for metastasis of ovarian cancer.