Curcumin suppresses malignant behaviors of ovarian cancer through regulation of tumor-associated macrophages.

Abstract

Curcumin, a natural polyphenol with established anti-tumor properties, has shown therapeutic potential in ovarian cancer. However, its mechanisms, particularly through modulation of tumor-associated macrophages (TAMs) in the tumor microenvironment, remain unexplored. This study aimed to elucidate how curcumin suppresses ovarian cancer progression by regulating TAM polarization. Primary TAMs isolated from ascites of ovarian cancer patients were co-cultured with SKOV3/OVCAR-3 cancer cells. Curcumin was administered at varying doses (5-80 μM) to assess its direct effects on cancer cell viability and its indirect effects via TAM modulation. Epithelial-mesenchymal transition (EMT), migration, invasion, and cytokine profiles were analyzed using CCK-8, flow cytometry, RT-PCR, Western blot, and functional assays. High-dose curcumin (40-80 μM) directly inhibited cancer cell proliferation. In contrast, low-dose curcumin (5-20 μM) suppressed TAM-induced malignant behaviors: it reduced M2 polarization (CD206⁺ TAMs decreased by 54.89% to 32.14%, p < 0.01) while increasing M1-associated cytokines (IL-12↑, IL-1β↑) and decreasing M2 markers (IL-10↓, TGF-β↓). TAM-conditioned medium primed with 20 μM curcumin significantly attenuated cancer cell migration (scratch closure: 65% vs. 85% in TAM-only group, p < 0.01), invasion, and EMT (E-cadherin↑, N-cadherin↓, Vimentin↓). Our study uncovered the mechanism of the anti-tumor effect of curcumin in low doses related to the regulation of TAMs, which might provide novel insight into the treatment of ovarian cancer.