Combined Effects of PC002 and Anticancer Drugs in Ewing's Sarcoma Cells

Abstract

Ewing's Sarcoma is a rare malignant tumor that grows in bones or nearby soft tissues. Current treatment focuses on chemotherapy, radiation therapy, and surgery, yet chemoresistance is common and remains the leading cause of treatment failure. PC002 is recently found effective in treating Ewing's Sarcoma in vitro and in vivo. However, the mechanism of action of PC002 is still under dispute, and no experiments have been conducted to explore its combination therapy in Ewing's Sarcoma cells. Thus, this study was performed to elucidate the mechanism of action of PC002 and facilitates the selection of future combination therapies for Ewing's Sarcoma. Vincristine, ABT-199, ABT-263, and Olaparib were combined with PC002. High-throughput screening and Fluorescence-activated Cell Sorting tests were performed in the A673 Ewing cell line to examine the drugs’ effects on inhibiting cell proliferation and inducing apoptosis. The results suggest that there was no antagonism between PC002 and these drugs. We discovered that the combination of PC002 and ABT-263 is highly synergistic (p<0.001), which should be further explored as a promising combination drug. The combinations of PC002 with Vincristine and with Olaparib are also potential therapeutic tools in combating chemoresistance and increasing the efficacy of the drugs in Ewing's Sarcoma.