Novel combinatorial treatment effects on SP1 and Survivin in Ewing Sarcoma

Purpose: Ewing Sarcoma (ES) is a bone and soft tissue cancer affecting young adults and children. ES most occurs in the bones or soft tissue of the arms, legs, and pelvis. Localized ES presents with 5-year survival rate of 70%, but metastatic 5-year survival rate is between 15% and 30%. Our laboratory is interested in combination treatments using less toxic agents to induce sensitization to chemotherapy in ES. The anti-cancer activity of a Non-Steroidal Anti-Inflammatory Drug, tolfenamic acid (TA), against ES cells has been shown. TA inhibits Specificity protein 1 (Sp1) and survivin, these markers are associated with aggressive cancer cell growth and resistance to chemo/radiation therapies. This studies purpose is to evaluate the effectiveness of TA and Copper-TA (Cu-TA) to inhibit ES cell growth alongside Vincristine (VCR). Methods: Anti-proliferative activity of TA or Cu-TA and/or (VCR) against ES cell lines, TC32 and CHLA258, was evaluated using CellTiterGlo kit. Dose curves were plotted and IC50 values were determined by Sigma-Plot software. The expression of Sp1 and survivin was determined by Western bot analysis. Results: When compared to TA, Cu-TA's IC50 values were significantly less. Cu-TA inhibited the expression of Sp1 and survivin in ES cells. The combination of Cu-TA and VCR showed higher efficiency for inhibiting ES cells. Conclusions: Cu-TA may effectively sensitize certain ES cells and induce the response of chemotherapy. Studies to understand the mechanism of action of Cu-TA are underway.