Red ginseng prevents niraparib-induced myelosuppression in C57BL/6 mice via inhibiting p53-mediated upregulation of p21 and p27.

Abstract

Myelosuppression is a serious and common complication of targeted therapy for cancer patients, and there are few studies exploring the efficacy of natural drugs in this condition. Niraparib is a widely used targeted therapy for the treatment of advanced ovarian cancer. As a poly (ADP-ribose) polymerase (PARP) inhibitor, niraparib significantly improves progression-free and overall survival in patients. We aimed to explore the potential effect of red ginseng (RG) on niraparib-induced myelosuppression and to further reveal its possible molecular mechanism. Female C57BL/6 mice were divided into control, tumor, model, and RG groups (n = 6). After receiving ID8 ovarian cancer cell inoculation, the mice received niraparib treatment (80 mg/kg) for 3 days. Meanwhile, RG groups (100 and 200 mg/kg) were intragastrically treated with RG extract for 7 days. Compared with the model group, RG extract increased the counts of peripheral blood cells and enhanced the hematopoietic function of bone marrow. Furthermore, RG extract increased the colony yield of hematopoietic progenitor cells (HPCs), facilitated DNA damage repair, alleviated the G0/G1 phase cell cycle arrest, and significantly reversed the increased expression levels of p53, p21, and p27, while stimulating cyclinE1 expression levels. These findings indicate that RG might have therapeutic potential on niraparib-induced myelosuppression, which encourages further clinical trials. This study is the first to explore the efficacy and mechanism of RG in preventing myelosuppression induced by niraparib.