Scoparone attenuates PD-L1 expression in human breast cancer cells by MKP-3 upregulation

초록

Cancer immunotherapy has recently achieved significant success, providing a new approach to anti-tumor treatment. However, some patients are susceptible to developing drug resistance, leading to unfavorable treatment outcomes. Therefore, in addition to blocking the interaction between PD-L1 and PD-1, other approaches are needed, such as down-regulating PD-L1 expression and promoting the degradation of PD-L1. Scoparone (SCO) is a bioactive compound isolated from Artemisia capillaris and possesses anti-tumor activity. However, the effect of SCO on PD-L1 expression in cancer has not been authenticated. The aim of this study was to evaluate the role of SCO in PD-L1 expression in breast cancer cells in vitro. Our results showed that SCO resulted in the down regulation of PD-L1 in breast cancer cells in a dosage dependent manner. SCO reduced PD?L1 expression through AKT inhibition. Interestingly, SCO treatment did not alter PTEN expression. However, it increased MKP-3 expression. In addition, the decrease in PD-L1 caused by SCO treatment was restored through siRNA-mediated knockdown of MKP-3. Taken together, these findings suggest that SCO inhibits the expression of PD-L1 in breast cancer cells by up-regulating MKP-3. Thus, SCO could serve as an innovative combinatorial agent for cancer immunotherapy. This study was supported by a grant of the Korea Health Technology R&D Project through the Korea Health Industry Development Institute (KHIDI), funded by the Ministry of Health & Welfare, Republic of Korea (grant number: HI22C1989).