Figure 7.

CAF inhibition by ripretinib blocks growth of OCCC in combination with carboplatin

(A) Inhibition of CAFs cultured for 7 days grown on attachment culture conditions in the presence of the indicated TKIs or carboplatin (1 μM). The data are presented as mean ± SD (n = 3). p values were determined by Student’s t test. Statistically significant differences are indicated: ∗p < 0.05, ∗∗p < 0.01.

(B) Inhibition of CAFs by ripretinib. CAFs co-cultured with cancer cells under co-culture conditions were treated with the indicated concentrations of ripretinib and carboplatin for 7 days (n = 3). ∗∗∗p < 0.001.

(C) Co-operative inhibition of the growth of co-cultivated cancer cells (OVN-48) by ripretinib and carboplatin. Cancer cells co-cultured with CAFs were treated for 7 days with the indicated concentrations of ripretinib and carboplatin.

(D) Fluorescence images of cancer cells and CAFs co-cultured for 7 days in the presence or absence of 100 μM carboplatin and/or 5 μM ripretinib. Scale bars, 100 μm.

(E) Cancer cells grown under monoculture conditions were treated with the indicated concentrations of ripretinib and carboplatin for 7 days (n = 3). ∗p < 0.05.

(F) Xenografted tumors (OVN-48, 49 days after co-transplantation of cancer cells and CAFs) were treated with the indicated combinations of carboplatin and/or ripretinib, and tumor volume (mean ± standard error of the mean) was measured weekly (n = 8). ∗∗∗p < 0.001.

(G) Immunostaining of xenograft tumors (78 days post transplantation) with HIF-1α. Magnified images are shown on the right. Scale bars, 500 μm (right) and 100 μm (left).

(H) Boxplots showing the percentage fraction of HIF-1α-positive cancer cells in the tumor tissues shown in (G). Average values ± SEM are shown. p values were determined by Student’s t test. Statistically significant differences are indicated: ∗p < 0.05, ∗∗p < 0.01, ∗∗∗p < 0.001.