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Effect of Disulfiram on gene expression of cytokines secreted by tumor-associated macrophages |
ZHANG Wenwen1 LIU Luyao1 CAO Juan1 LI Weibo1 DONG Chunling2 LI Bo1 |
1.Experimental Teaching Center, Hospital of Stomatology, Jilin University, Jilin Province, Changchun 130021, China;
2.Department of Respiratory Medicine, the Second Hospital of Jilin University, Jilin Province, Changchun 130041, China |
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Abstract Objective To study the effect of Disulfiram (DSF) on the genes expression of cytokine secreted by tumor-associated macrophages (TAMs) in oral squamous cell carcinoma (OSCC) tumor cell supernatant. Methods RAW264.7 cells were randomly divided into control group and research group. Two induction methods were used, the first inducement was that CAL27 tumor cell supernatant was used to induce RAW264.7 cells for 48 h in control group; and DSF and copper gluconate (DSF/Cu) 2 μmol/L were added to the CAL27 tumor cell supernatant to induce RAW264.7 cells for 48 h in research group. The second inducement was that RAW264.7 cells were induced with CAL27 tumor cell supernatant for 48 h, and then continued to be induced for 48 h in control group; in research group, after CAL27 tumor cell supernatant induced RAW264.7 cells for 48 h, DSF/Cu 2 μmol/L was used to intervene for 48 h. The gene expression levels of nitric oxide synthase (iNOS), interleukin-12 (IL-12), tumor necrosis factor-α (TNF-α), argininase 1 (Arg-1) and IL-10 were measured. Results DSF/Cu was added in the induction process, iNOS mRNA level of research group was higher than that of control group, Arg-1 mRNA level was lower than that of control group, and the differences were highly statistically significant (all P < 0.01). There were no significant differences in IL-12, TNF-α and IL-10 mRNA levels between two groups (P > 0.05). DSF/Cu was added 48 h after induction, iNOS mRNA, IL-12 mRNA, TNF-α mRNA, IL-10 mRNA levels in research group were higher than those in control group, and Arg-1 mRNA level was lower than that in control group, with statistically significant differences (P < 0.05 or P < 0.01). Conclusion DSF can regulate the gene expression of cytokines secreted by TAMs, which helps to further clarify the mechanism of disulfiram against OSCC. It may provide experimental basis and treatment strategies for the diagnosis and treatment of oral tumors in the future.
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