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. Author manuscript; available in PMC: 2021 Nov 26.
Published in final edited form as: Sci Transl Med. 2021 May 26;13(595):eabe8226. doi: 10.1126/scitranslmed.abe8226

Figure 3. Effects of H6PD loss on sensitivity to enzalutamide therapy and tumor corticosterone concentrations in mouse xenograft models.

Figure 3.

(A and E) H6PD loss and the inhibitory effect of enz on A, LAPC4 and E, VCaP xenograft tumor growth. (B and F) H6PD loss and progression-free survival in enz-treated B, LAPC4 and F, VCaP xenografts. For both xenograft studies, cells with H6PD gRNA (gH6PD) or control gRNA (gNC) were grown in orchiectomized mice supplemented with DHEA and arbitrarily assigned to enz or chow (Ctrl). Tumor volume was compared between gH6PD/Enz and gNC/Enz with an unpaired two-tailed t-test on day 20 (LAPC4) or day 29 (VCaP). Progression-free survival was compared between gH6PD/Enz and gNC/Enz with a log-rank test. The number of mice in the LAPC4 gNC/Ctrl, gNC/Enz, gH6PD/Ctrl and gH6PD/Enz groups were 8, 8, 9, and 11, respectively. The number of mice in the VCaP gNC/Ctrl, gNC/Enz, gH6PD/Ctrl and gH6PD/Enz groups were 9, 10, 9, and 9, respectively. (C and G) Effects of H6PD knockout with and without enz treatment on the absolute concentration of corticosterone (active glucocorticoid in mice) in C, LAPC4 and G, VCaP xenograft tumors. (D and H) The absolute concentration of corticosterone in sera by treatment group, with and without H6PD loss in mice with D, LAPC4 and H, VCaP xenografts. For all panels unless otherwise noted, error bars represent the SEM; p values were calculated using unpaired 2-tailed t tests.