Sulconazole inhibits PD-1 expression in immune cells and cancer cells malignant phenotype through NF-κB and calcium...

Area of Science:

• Immunology
• Oncology
• Pharmacology

Background:

• Programmed death-1 (PD1) overexpression on T-cells facilitates cancer immune evasion.
• Anti-PD-1/PDL-1 therapies have improved cancer treatment but show variable efficacy.
• Novel adjunct therapies are needed to overcome treatment resistance and enhance anti-tumoral immune responses.

Purpose of the Study:

• To investigate the potential of the antifungal drug Sulconazole (SCZ) in modulating immune responses and cancer cell behavior.
• To explore SCZ's effect on PD-1 expression and its underlying signaling pathways.
• To evaluate SCZ's impact on cancer cell proliferation, migration, and tumor growth.

Main Methods:

• Assessed PD-1 expression at RNA and protein levels in activated PBMCs and T cells treated with SCZ.
• Investigated the effect of SCZ on NF-κB and calcium signaling pathways.
• Evaluated SCZ's impact on cancer cell proliferation, migration, and tumor growth in a zebrafish embryo model.
• Measured SCZ's effect on calcium mobilization in cancer cells.

Main Results:

• SCZ significantly inhibited PD-1 expression on activated PBMCs and T cells at both RNA and protein levels.
• SCZ repressed NF-κB and calcium signaling pathways crucial for PD-1 induction.
• SCZ treatment reduced cancer cell proliferation and migration.
• SCZ inhibited tumor growth in zebrafish embryos and suppressed calcium mobilization in cancer cells.

Conclusions:

• Sulconazole demonstrates therapeutic potential as a monotherapy or adjunct strategy for cancer treatment.
• SCZ may prevent T-cell exhaustion by inhibiting PD-1 expression.
• SCZ represses cancer cell malignant phenotypes, potentially improving tumor eradication.