Fig. 6: HSP70 inhibitor JG231 suppresses NEPC xenograft tumor growth.
a CWR22Rv1, H660, UCDCaP-CR, RWPE-1, and IMR90 cells were treated with increasing doses (0.001, 0.01, 0.1, 0.25, 0.5, 1, 2.5, 5, and 10 µM) of JG231 for 3 days, and the viable cells were counted. Results were compared to controls to generate cell viability. b Organoids from LuCaP93 PDX were treated with JG231 (0.01, 0.05, 0.1, and 0.25 µM) for 7 days. Cell viability was assayed by the CellTiter-Glo Luminescent assay and the live and dead cells were visualized by immunofluorescence (n = 3 independent samples). Statistical significance was determined by one-way ANOVA with a Turkey multiple-comparison test. Scale bar represents 100 microns. c, d Mice bearing LuCaP93 xenografts were treated with vehicle control, or JG231 (4 mg/Kg i.p) for 30 days (n = 9). Tumor volumes were measured twice weekly (c). Tumors were photographed and weighed (d). Data represented means ± S.D. from 9 tumors per group. Statistical significance was determined by unpaired two-sided t-test on day 32. e IHC staining of N-Myc and Ki67 in each group was performed. Scale bar represents 20 microns. f Mice bearing H660 xenografts were treated with vehicle control, or JG231 (4 mg/Kg i.p) for 40 days (n = 6). Statistical significance was determined by unpaired two-sided t-test on day 40. g IHC staining of N-Myc and Ki67 in each group was performed. Scale bar represents 20 microns. h H/E staining of kidneys and livers in each group was performed. Scale bar represents 100 microns. i, j Gene Ontology (GO), Kyoto Encyclopedia of Genes and Genomes (KEGG), and Reactome analyses illustrate the up-regulated and down-regulated pathways in H660 cells treated with 5 µM JG231 for 24 h. k Gene Set Enrichment Analysis (GSEA) showing the enrichment of Rickman’s 966 N-Myc Bivalent genes in H660 cells treated with JG231. Results are the mean of three independent experiments ( ± S.D.). Source data are provided as a Source Data file.
