Fig. 6
PX-12 treatment reduces CRPC tumor growth by LNAI cells. a PX-12 treatment of castrated male Nu/Nu mice injected with LNAI cells. Mean profiles of tumor growth for each group were obtained using linear mixed model with random intercepts and slopes. Adjusted areas under the curve (aAUCs) are plotted within the inset for the DMSO group (n = 8) and the PX-12-treated group (n = 7). Note that one tumor in the PX-12 group was dropped following outlier analysis via Grubbs’ test. The red arrow denotes a complete responder tumor, which did not recur even after cessation of drug treatment. The p-value was determined via a permutation test of the ratio of the two aAUCs. b Fold-changes in tumor size and PSA levels from PX-12-treated tumors, normalized to values from DMSO-treated tumors. c Representative images of H&E and immunohistochemical staining for Ki67 in the two treatment groups. Two separate tumors per group are shown. Tumor volumes are noted for each tumor sample. Size bars, in white, are relevant for each panel and represent a 100 µm scale. d TUNEL staining to indicate apoptosis. The TUNEL assay was carried out on tissue sections from control and PX-12-treated tumors. Representative staining images of dUTP, DAPI, and co-localized dUTP/DAPI staining are shown for two separate representative tumors in each group. Images were acquired through identical exposures per channel. The size bar, in white, is relevant for each panel and represents a 50 μm scale. e Representative images of immunohistochemical AR staining from the two treatment groups. Two separate tumors per group are shown. The size bar, shown in white, is relevant for each panel and indicates a 100 µm scale. f Western blot of total protein lysates (25 µg) from the indicated LNAI tumor treatment groups. Blots were probed with the denoted antibodies. Both sets of western blots were run and developed under identical conditions. The asterisk denotes the sole non-responder tumor in the treatment group, which is the statistical outlier referenced in (a). g Schematic of AR-induced redox stress as a putative “Achilles’ heel” in CRPC and the protective function of TRX1 in mitigating this stress
