Fig. 5 DDO-5936 dose-dependently impairs the growth of xenografted HCT116 cells in nude mice. DDO-5936 dose-dependently impairs the growth of xenografted.

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Fig. 5 DDO-5936 dose-dependently impairs the growth of xenografted HCT116 cells in nude mice. DDO-5936 dose-dependently impairs the growth of xenografted HCT116 cells in nude mice. (A) Body weights of nude mice treated with either vehicle or DDO-5936 are shown. Body weight is plotted as the means ± SEM (n = 6 mice for each group). (B) Volume measurements of HCT116 xenograft tumors treated with vehicle, DDO-5936 (50 mg/kg per day), or DDO-5936 (100 mg/kg) for 21 days. DDO-5936 was administered by intraperitoneal injection once a day. Tumor volume is plotted as the means ± SEM (n = 6 mice for each group) (**P < 0.01, ***P < 0.001, paired Student’s t test, two-tailed). (C) Volume distribution of HCT116 xenograft tumors treated with vehicle or DDO-5936 at 21 days. (D) Western blot analysis of Hsp90, Hsp70, GR, p-GR, AKT, p-AKT, ERK1/2, p-ERK1/2, CDK4, and CDK6 in three representative xenograft tumor tissue samples from each group. β-Actin was used as a loading control. Data are representative of three technical replicates. (E) Schematic model of the process in which DDO-5936 modulates the Hsp90-Cdc37 chaperone cycle. DDO-5936 inhibited the Hsp90-Cdc37 PPI through binding to a previously unknown pocket on Hsp90 involving E47, a binding determinant of the Hsp90-Cdc37 complex, inhibiting the maturation of the kinase client to implement the antiproliferation effects of HCT116 cells. Lei Wang et al. Sci Adv 2019;5:eaax2277 Copyright © 2019 The Authors, some rights reserved; exclusive licensee American Association for the Advancement of Science. No claim to original U.S. Government Works. Distributed under a Creative Commons Attribution NonCommercial License 4.0 (CC BY-NC).