Fig. 3: A subset of SCLC lines upregulates mTOR signaling genes and is sensitized to mTOR inhibitors in response to JIB-04 treatment.
From: Jumonji histone demethylases are therapeutic targets in small cell lung cancer
A SCLC cell lines (H2171 and H524) upregulated mTOR signaling pathway genes upon treatment with JIB-04 at 0.05 µM as determined by GSEA analysis. Nominal p-values are shown as calculated on the GSEA site following Subramanian et al. [61]. See Supplementary Information RNA-seq dataset for more details. B Dose-response curves to each of two different mTOR inhibitors alone and concurrently with low dose of JIB-04 (IC25) measured by MTS viability assays over a 4-day treatment. The two cell lines that upregulated mTOR signaling genes in response to JIB-04 have 2–3-fold or greater enhanced sensitivity to mTOR inhibitors (mean ± SEM is shown for each dose, n = 3–4). C HCC4001 which did not significantly upregulate mTOR signaling genes in response to JIB-04, did not show enhanced sensitivity to mTOR inhibitors (mean ± SD is shown for each dose, n = 8). B, C JIB-04 IC25 = 0.25 µM for H2171 and H524, 0.01 µM for HCC4001. P-values for curve comparisons calculated by GraphPad Prism (top, bottom, IC50, Hill coefficient) are as follows: H2171 Samotolisib ± JIB-04 0.0069; H2171 Torkinib ± JIB-04 < 0.0001, H524 Samotolisib ± JIB-04 0.0005, H524 Torkinib ± JIB-04 0.0011, HCC4001 Samotolisib ± JIB-04 0.1425, HCC4001 Torkinib ± JIB-04 0.1932.
