Abstract: Objective: To investigate the effect of curcumin on the gene expressions of cytokines secreted by tumor-associated macrophages (TAMs) induced by the supernatants of the oral squamous cell carcinoma (OSCC) cells (Cal27 cells), and to clarify the mechanism of curcumin's anti-OSCC effect. Methods: The Raw264.7 cells were randomly divided into control group and different concentrations (1.25, 2.50, 5.00, 10.00, 20.00 and 40.00 μmol·L^-1) of curcumin groups. The cells from each group were added with Cal27 cell supernatants and incubated for 48 h, and the cell activities were detected by CCK-8 assay. The Raw264.7 cells were randomly divided into control group and different concentrations (5, 10 and 20 μmol·L^-1) of curcumin groups. The cells from each group were added with Cal27 cell supernatants and incubated for 36 and 48 h, and Real-time PCR method was used to detect the mRNA expression levels of interleukin-12 (IL-12), inducible nitric oxide synthase (iNOS), tumor necrosis factor-α (TNF-α) and interleukin-10 (IL-10) in the cells in various groups. After the Raw264.7 cells were incubated with Cal27 cell supernatants for 48 h, the cells in curcumin groups were treated with different concentrations (5, 10 and 20 μmol·L^-1) of curcumin for 48 h, and Real-time PCR curcumin method was used to detect the mRNA expression levels of IL-12, iNOS, TNF-α, IL-10 and Arginase 1 (Arg-1) in the cells in various groups. Results: Compared with control group, the cell activity of Raw264.7 cells in 40 μmol·L^-1 curcumin group was significantly reduced (P<0.01). After the Raw264.7 cells were incubated with different concentrations of curcumin and Cal27 cell supernatants for 36 h, compared with control group, the IL-12 mRNA expression level in 20 μmol·L^-1 curcumin group was increased (P<0.01); the iNOS and TNF-α mRNA expression levels in the Raw264.7 cells in 10 and 20 μmol·L^-1 groups were significantly decreased (P<0.05 or P<0.01); the IL-10 mRNA expression level in 20 μmol·L^-1 group was decreased (P<0.01). After the Raw264.7 cells were incubated with different concentrations of curcumin and Cal27 cell supernatants for 48 h, compared with control group, the IL-12 mRNA expression levels in the Raw264.7 cells in 5 and 20 μmol·L^-1 groups were increased (P<0.01); the iNOS TNF-α and IL-10 mRNA expression levels in 5 and 20 μmol·L^-1 groups were decreased (P<0.01). After the Raw264.7 cells were incubated with Cal27 cell supernatants for 48 h, and intervented with different concentrations of curcumin, compared with control group, the IL-12 mRNA expression levels in 10 and 20 μmol·L^-1 curcumin groups were increased (P<0.01); the iNOS, TNF-α and Arg-1 mRNA expression levels in the Raw264.7 cells in different concentrations of curcumin groups were decreased (P<0.05 or P<0.01); the IL-10 mRNA expression level in the Raw264.7 cells in 20 μmol·L^-1 curcumin group was significantly reduced (P<0.01). Conclusion: Curcumin can regulate the mRNA expression levels of cytokines IL-12, iNOS, TNF-α, IL-10 and Arg-1 secreted by TAMs at different stages of TAMs induction.

Key words: curcumin, tumor-associated macrophages, cytokine, oral squamous cell carcinoma