Fig. 7
Optimization of SCR130 treatment. (A) Comparison of cell death and cell cycle distribution resulting from (I) standard treatment (see Figs. 2, 3, 30 µM SCR130) with two different alternative treatment schemes in Cal33 and HSC4. (II) Treatment with liposomes: liposomes were loaded with 10 mM SCR130 solution and diluted according to the standard treatment 1:333. Each value represents mean ± SD (n = 2). (III) Reverse treatment: 30 µM SCR130 were added 3 h after application of 2 Gy IR instead before. Each value represents mean ± SD (n = 2). All the other steps were carried out according to the standard treatment. Control: DMSO according to 30 µM SCR130 (I and III), unloaded liposomes diluted 1:333 in the treated volume (II); 2 Gy: 2 Gy IR; SCR130: 30 µM SCR130 (I and III), 1:333 dilution of liposomes loaded with 10 mM SCR130 in the treated volume (II); combination: combination of SCR130 and 2 Gy IR according to the treatment scheme. (B) Colony formation assay: Treatment of HSC4 with 30 µM SCR130 and increasing single doses of IR up to 8 Gy (instead of 2 Gy) according to the standard treatment. The control was treated with the same volume DMSO as used 30 µM SCR130 and was used for calculating the SF. Normalized data to DMSO control and linear quadratic fit of 0 µM and 30 µM SCR130 are shown. Each value represents mean ± SD (n = 4). (C) Overall survival of patients with HNSCC and breast cancer depending on their ligase IV expression (mRNA data from RNA seq). Data and analysis from publicly available Kaplan-Meier Plotter database37.
