1. EPHA2 inhibitors inhibit phosphorylation of AKT and ERK, arrest cell cycle at G0–G1, and induce apoptosis in both vemurafenib (VEM)-sensitive and VEM-resistant cells.
EPHA2 inhibitors inhibit phosphorylation of AKT and ERK, arrest cell cycle at G0–G1, and induce apoptosis in both vemurafenib (VEM)-sensitive and VEM-resistant cells. ALW-II and HG abrogated EPHA2–AKT and EPHA2–MAPK signaling in both vemurafenib-sensitive A375 (A) and A375-P (B) cells, whereas vemurafenib inhibited only the MAPK pathway and only in the parental A375 line. Similarly, ALW-II and HG caused both G0–G1 arrest and sub-G1 fractionation in both vemurafenib-sensitive A375 (C) and A375-P (D) cells. However, vemurafenib only induced G0–G1 arrest and exclusively in the A375-sensitive line. Error bars, percentage of cells ± SEM (n = 2). E, ALW-II and HG caused nuclear condensation and fragmentation in both A375 (vemurafenib-sensitive) and CHL-1 (vemurafenib-resistant) cells. The nuclei were stained with Hoechst, and analyzed using a fluorescent microscope (the condensed/fragmented nuclei are indicated by arrowheads). F and G, quantification results for the nuclei staining in E.
Benchun Miao et al. Cancer Discovery 2015;5:
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