Fig. 5 | Nature Communications

Fig. 5

From: CDK4/6 inhibitors target SMARCA4-determined cyclin D1 deficiency in hypercalcemic small cell carcinoma of the ovary

Fig. 5

Palbociclib is effective in suppressing SCCOHT tumor growth in vivo. Palbociclib significantly suppresses tumor growth in xenograft models of BIN-67 (a, b, e, f) and SCCOHT-1 (c, d, g, h), as well as a patient-derived xenograft (PDX) model of SCCOHT (i). After tumor establishment (3–4 weeks for BIN-67 and SCCOHT-1; 3 months for the PDX), mice were treated daily with vehicle (ctrl) or palbociclib (palbo) for the indicated days. a, c Tumor volume fold change from Day 1 of treatment in BIN-67 (a, n = 5 per group) and SCCOHT-1 (d, n = 4 for vehicle, n = 5 for palbociclib; 150 mg kg−1) models (two-way ANOVA, ****p < 0.0001). b, d The final tumor volume and weight measured at necropsy in BIN-67 (b, n = 8 per group) and SCCOHT-1 (d, n = 4 for vehicle, n = 5 for palbociclib) models (two-tailed t test, ****p < 0.0001, **p < 0.01). eh Palbociclib treatment resulted in suppression of RB phosphorylation, Ki67 expression, and mitotic index in BIN-67 and SCCOHT-1 xenograft tumors of the trial end points. Representative images of IHC (p-RB, Ki67) and hematoxylin and eosin (H&E) analysis of BIN-67 (e) and SCCOHT-1 (g) xenograft tumor tissues. Quantification results of p-RB, Ki67, and mitotic count of BIN-67 (f, n = 3) and SCCOHT-1 (h, n = 4). In the H&E images, black arrows point to mitotic active cells as an example. Bar 50 µm; two-tailed t test, *p < 0.05, **p < 0.01, ***p < 0.001, ****p < 0.0001. i Tumor volume fold change from Day 1 of treatment in the SCCOHT PDX model (n = 6 for vehicle, n = 3 for palbociclib). Mice were treated with the initial dose of 150 mg kg−1 of palbociclib. After first signs of any animal discomfort, we reduced the dose to 100 mg kg−1. Mice that showed weight loss were not included for the analysis. Two-way ANOVA, **p < 0.01. Error bars: mean ± standard error of mean (s.e.m.)

Back to article page