Figure 5
From: XI-006 induces potent p53-independent apoptosis in Ewing sarcoma
Inhibition of PARP potentiates the cytotoxic effects of XI-006
a) TC252, RD-ES and WE-68 were pre-treated with olaparib (0.5 or 1 μM) or vehicle control (DMSO) for 2 hrs, prior to the addition of XI-006 (0–5 μM). Cell viability was determined through 7AAD staining (24 and 48 hrs post XI-006 treatment) and analysed by flow cytometry. Data represents average percentage cell death ± STDEV from duplicate reactions. Asterisk denotes significant increase in apoptosis compared to XI-006 alone (*15–30%, **31–45%, ***>46% increase). (b) STA-ET-1, RDES, WE-68 and U20S cells were treated with XI-006 (0.5, 1.25, 2.5 μM) for 4 and 8 hrs. mRNA expression levels of Mre11 were determined through real-time qPCR analysis. Data represents mean expression (fold change) ± SE from triplicate reactions. (c) RD-ES cells were pre-treated with Olaparib for 2 hrs prior to the addition of XI-006 (0.5, 1, 2 μM) for an additional 4 hrs. Mre11 mRNA expression levels determined as in (b). Asterisk denotes statistical significant reduction in expression compared to either vehicle control (b) or XI-006 treatment alone (c) (*P < 0.05, **P < 0.01, ***P < 0.001, ****P < 0.0001).
