Inhibition of lung cancer cell proliferation and viability by CYT387.

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Presentation transcript:

Inhibition of lung cancer cell proliferation and viability by CYT387. Inhibition of lung cancer cell proliferation and viability by CYT387. A, crystal violet stain of A549 cell clonogenic assay after 10-day treatment with dimethyl sulfoxide (DMSO), 2.5 μmol/L MRT67307, CYT387, or ruxolitinib. B, dose-response to MRT67307 or CYT387 treatment at 72 hours normalized to DMSO control, mean ± SEM of quadruplicate samples shown. Blue, KRAS-mutant/dependent cell lines; red, KRAS-WT/independent cell lines. C, cell viability of 12 KRAS-dependent (blue) or independent (red) lung cancer lines (purple, KRAS-WT/dependent) treated with 5 μmol/L inhibitors for 72 hours normalized to DMSO control. Plotted are relative cell line sensitivities for MRT67307/BX795 and AZD6244/CI-1040 (top), or CYT387/MRT67307 and CYT387/AZD6244 (bottom). *, P < 0.05, Pearson correlation. D, normalized relative CYT387 sensitivity in the same NSCLC lines compared with 17 other targeted inhibitors at 5 μmol/L. Nearest neighbor analysis by Pearson correlation, *, P < 0.05. E, phase-contrast images (×20) of A549 spheroids cocultured with HUVECs and treated with DMSO, MRT67307, CYT387, or ruxolitinib (1 μmol/L) for 18 or 36 hours. Mean number and SD of dispersed cells per spheroid from triplicate devices shown. F, phase-contrast images (×20) of A549 spheroids stimulated with EGF and treated with DMSO or 1 μmol/L CYT387 for 36 hours. Mean number and SD of dispersed cells per spheroid from triplicate devices shown. Zehua Zhu et al. Cancer Discovery 2014;4:452-465 ©2014 by American Association for Cancer Research