Promoting tumor cell secretion of IL18 to induce reprogramming of tumor-associated macrophages – The novel anticancer mechanism of anlotinib in ovarian cancer
Ovarian cancer represents a formidable challenge to female reproductive health, mainly due to a marked propensity for intraperitoneal implant metastasis, as well as a lack of effective therapeutic strategies. Anlotinib, a multi-targeted receptor tyrosine kinase inhibitor, has demonstrated anti-tumor effects across various tumors and promising clinical outcomes in ovarian cancer. However, the underlying molecular mechanisms of anlotinib on tumor-associated macrophages (TAMs) within the ovarian tumor microenvironment have not been completely elaborated yet. In this study, we demonstrated that anlotinib suppressed the proliferation, migration, and invasion ability of ovarian cancer cell line ID8 through in vitro experiments. By co-culturing ovarian cancer cells with human mononuclear macrophage THP-1 or murine (RAW264.7) monocyte-derived macrophages, we observed that anlotinib promoted M1 macrophage polarization while simultaneously inhibiting M2 phenotype polarization of TAMs. Further in vitro experimentation revealed that anlotinib polarized TAMs to M1 macrophages by upregulating the expression of interleukin 18. Finally, we validated the antitumor efficacy of anlotinib in vivo and its ability to reprogram TAMs using an orthotopic ovarian cancer model established with the murine ovarian cancer cell line ID8.