METFORMIN DECLINES PD-L1 EXPRESSION VIA DOWN-REGULATING HISTONE H3K9 ACETYLATION

Introduction: Metformin has recently received increasing attention for its potential function in suppression of cancer cell growth, but the underlying mechanism remains far from completely understood. PD-L1 was demonstrated as a potential strategy against multiple malignancies. However, whether metformin is associated with PD-L1 in antitumor function remains to be elucidated.Materials and Methods: Western blots were used to detect the expression of PD-L1 and histone H3 acetylation in 0, 5, 10 mM metformin treated A549 cells; Meanwhile, the PD-L1 transcription was quantitated by qRT-PCR; Furthermore, ChIP analysis was performed to investigate H3 acetylation in PD-L1 at the treatment of metformin.Results: Metformin declined histone H3K9 acetylation resulting in downregulation of PD-L1 expression. Specifically, in metformin treated A549 cells, the H3K9 acetylation was significantly decreased, the less acetylated H3K9 in the nucleosome at the PD-L1 region blocked PD-L1 transcription resulting in low expression of PD-L1.Conclusion: This study would facilitate elucidation of the metformin functioning mechanism in inhibiting tumor proliferation.

Automated summary

Metformin's potential role in inhibiting cancer cell growth has gained attention, but its underlying mechanism is not fully understood. PD-L1 has been identified as a potential strategy against multiple malignancies. However, the association between metformin and PD-L1 in anti-tumor function needs to be elucidated.