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

Xiaogang Xia, Ting Li^*

Department of Laboratory, Hanchuan People's Hospital, Hanchuan 431600, Hubei Province, China

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.