The combination of BET and METTL3 inhibitors elicits synergistic antitumor effects in ovarian cancer cells via reducing SP1 and BCL-2 expression
Ovarian cancer (OC) remains a major health threat to woman despite treatment advances. New therapeutic strategies are demanded to persistently explored. In this study, we found that inhibitors of bromodomain and extra-Terminal domain (BET) and methyltransferase-like 3 (METTL3) exerted synergistic proliferative inhibition in different OC cell lines. In vitro synergism was translated into in vivo antitumor activity through the combination of BET inhibitor HJP-178 and METTL3 inhibitor STM2457. Mechanistically, this combination mainly enhanced apoptosis rather than affecting cell cycle arrest. Furthermore, it was revealed that HJP-178 decreased the transcription of Specificity protein 1 (SP1) while STM2457 lowered the N