Quinine modulates PD-L1 and STAT3 in MCF-7 cells: An in silico and in vitro study

Abstract

Programmed death-ligand 1 (PD-L1) overexpression in cancer cells is linked to immune escape and tumor progression, with signal transducer and activator of transcription 3 (STAT3) as a key transcription factor regulating its expression. This study evaluates the potential of quinine (QN), traditionally used for malaria, to target PD-L1 and STAT3 in MCF-7 breast cancer cells. The binding affinities of QN to PD-L1 and STAT3 were assessed using molecular docking. The effects of QN on PD-L1 and STAT3 gene expression were assessed via real-time polymerase chain reaction. Cell viability, migration, and colony formation were evaluated using cell culture methods, and the protein levels of vascular endothelial cell growth factor (VEGF), tubulointerstitial nephritis antigen-like 1 (TINAGL-1), and epithelial cadherin (E-cadherin) were examined via Enzyme-linked immunosorbent assay (ELISA). QN exhibited selective cytotoxicity toward MCF-7 cells (IC50: 31.7 µM) while sparing healthy HME1 mammary epithelial cells. QN treatment led to a dose-dependent decrease in PD-L1 and STAT3 gene expression in MCF-7 cells. Migration and colony formation of MCF-7 cells were significantly inhibited at 30 µM QN, whereas HME1 cell migration was unaffected, indicating a selective reduction in cancer cell motility. ELISA results revealed statistically significant VEGF downregulation and TINAGL-1 upregulation in MCF-7 cells. These findings indicate that QN suppresses MCF-7 cell growth and migration by downregulating PD-L1 and STAT3 gene expression, reducing VEGF levels, and increasing TINAGL-1 levels, highlighting the compound’s potential for PD-L1 inhibition in cancer.