Anti-tumor activity of trimethoprim-sulfamethoxazole against melanoma skin cancer through triggering allergic reaction and promoting immunity.

The anti-cancer impact of an allergic reaction is strongly linked to immunity enhancement. Trimethoprim-sulfamethoxazole (TMP-SMX), an antibiotic, has potential immunomodulatory effects, but has side effects such as allergies. Thus far, the effects and underlying mechanisms of TMP-SMX in melanoma have not been clarified. This study examined the potential roles of TMP-SMX in melanoma skin cancer using an immunodeficient mouse model. TMP-SMX significantly improved the survival rate and reduced the tumor weight and growth and vascular endothelial growth factor levels in melanoma skin cancer of immunodeficient mice. In the forced swimming test, TMP-SMX significantly reduced immobility time compared to the melanoma skin cancer of immunodeficient mice, indicating improved immunity. TMP-SMX significantly increased infiltration of mast cells and release of allergy-related mediators (IgE, histamine, interleukin (IL)-4, IL-5, IL-13, and IL-33) and immune-enhancing mediators (tumor necrosis factor-α, IL-2, IL-6, and IL-12). In addition, the administration of TMP-SMX significantly increased the caspase-3, 8, and 9 activities. Furthermore, mice given TMP-SMX showed no adverse reactions according to the blood biochemical parameters. TMP-SMX significantly inhibits the growth of melanoma skin cancer by triggering an allergic reaction and promotingimmunity. Hence, we propose that TMP-SMX may be used as an immune booster in cancer chemotherapy.