Fig. 5: MKC8866 inhibits PCa tumor growth in syngeneic PCa mouse models.

A–C Myc-CaP cells were subcutaneously injected into FVB mice. A Schematic view of MKC8866 treatment. Mice were randomized and treated orally with vehicle (n = 7 mice, 14 tumors) or MKC8866 (300 mg/kg) (n = 7 mice, 14 tumors) once every two days. B Tumor volumes at indicated days and (C) tumor weights at the end of experiment. D–F Validation of Myc-CaP PTEN KO cell line by western analysis (inset). WT and PTEN KO cells were subcutaneously injected into FVB mice. D Tumor volumes are presented for WT and PTEN KO tumors (n = 5 mice each, 9 tumors per each group). E PTEN KO tumor weights were measured at day 16–18 when WT tumors were maximum 0.1 g, as indicated. F Myc-CaP WT and PTEN KO (n = 2 biological replicates per group) cells were subjected to qRT-PCR. G Association of PD-L1 and B7-H3 mRNA expression with IRE1α mRNA low (n = 160) and high (n = 129) samples in the TCGA PCa dataset. H MKC8866 treatment strategy for Myc-CaP PTEN KO or RM-1 models. Tumor volume for (I) Myc-CaP PTEN KO (vehicle and MKC8866, n = 8 mice each, 16 tumors per group) and (J) RM-1 (vehicle and MKC8866, n = 7 mice each, 14 tumors per group) models. Same as in (I and J), but tumor weights were measured at the end of the experiment for (K) Myc-CaP PTEN KO and (L) RM-1 models. Mean ± standard error by two-tailed student’s t test is presented for figure (B, C), C (p = 0.007), D (p = 1-06E-05 for day 16), E (p = 8.7E-07), I, K (p = 0.005), J, and L (p = 1.4E-05); unpaired two-tailed Mann Whitney t-test is used for figure (G); **p < 0.01, ***p < 0.001, ****p < 0.0001. Source data and exact p values are provided as a Source Data for figures (B, I, and J). In box-plots, whiskers represent 10–90 percentile and middle lines indicate median of the data. Figures 5A and 5H were created in BioRender. Unal, B. (2023) BioRender.com/u75i711.