Figure 4.
M17-B15 suppresses AR signaling to inhibit PSA expression and is efficacious in mouse xenograft tumor. M17-B15 and darolutamide antagonize FL-ARF876L (A) and FL-ARF876L/T877A (B) with Enz as the control. (C) Relative mRNA expression of PSA in LNCaP cells determined by qPCR. (D) M17-B15 reduces the endogenous PSA levels but does not affect the AR levels in LNCaP cells. The densities of the dimethyl sulfoxide (DMSO) groups were normalized to 1 for each ratio. (E) M17-B15 reduces the PSA levels of LNCaP cells secreted in the cellular media. (F) Nuclear and cytoplasmic extracts were collected from LNCaP cells. GAPDH and LaminB were used as the controls for the cytoplasmic fraction and nuclear fraction, respectively. The densities of the DMSO groups were normalized to 1 for each ratio. M17-B15 (2.5 mg/kg/week, n = 6 per group) significantly inhibited tumor volume (G) and tumor weight (H), versus vehicle control (n = 6 per group) and positive drug Enz (2.5 mg/kg/week, n = 6 per group). (I) Photographs of xenograft tumors harvested at day 29. (J) Body weight of mice in each group. (K) H&E staining of representative sections of xenograft tumors (bar = 100 μm). *P < 0.05, **P < 0.01 vs DHT group for in vitro assays or vs vehicle for in vivo assays; ns, not significant.