Although the therapeutic effect of poly-ADP-ribose polymerase (PARP) inhibitor, olaparib, was successful, the development of resistance was inevitable. Among ginsenosides, compound K (CK) has a higher absorption rate and has shown anti-tumor effects in various tumor. Therefore, we explored the effectiveness of a co-treatment with olaparib and the ginsenoside CK in castration-resistant prostate cancer (CRPC).

The effects of olaparib and CK were evaluated in vitro using cell viability, colony formation, cell cycle, apoptosis, and homologous recombination repair assay in 22Rv1, LNCaP, PC-3, and DU145 cells. The anti-tumor efficacy of co-treatment was verified in vivo using 22Rv1 and PC-3 cells.

Co-treatment with olaparib and CK reduced cell proliferation, migration, and invasion abilities. The effect of co-treatment was confirmed by detecting cell cycle arrest and expression of cell cycle regulatory proteins. Since the cell cycle is regulated by the DNA damage response, phosphorylated ataxia-telangiectasia mutate (ATM), ATM- and Rad3-related (ATR), as well as γH2AX and Rad51 expression were examined. We confirmed the inhibition of DNA repair and an increase in DNA damage-induced apoptosis; knockdown study using RNA interference revealed the same results. Finally, we verified that co-treatment increased the inhibition ratio of tumor volume, and further enhanced the anti-tumor effect by activating pro-apoptotic proteins.

Taken together, these findings provide evidence that CK interacts with olaparib to induce DNA damage and inhibit DNA repair. The co-treatment promotes apoptosis and inhibits tumor growth in CRPC. Thereby, our findings suggest that this dual therapy is a potential treatment strategy for CRPC.