7.

Telmisartan has synergistic effects with vemurafenib in vitro. (A) 5 × 5 dose matrix for vemurafenib x telmisartan combination in A375 cells. Percent growth inhibition is visualized using a color scale. The data in matrix are average of three experiments. Isobologram analysis for the combination effect of (B) ED90 (C) ED75 and (D) ED50, single doses of vemurafenib and telmisartan were used to draw the line of additivity. Green triangles represent single doses needed for the combination effect ED. Representative graphs (E) and quantification of three independent experiments (F) for apoptosis in A375 cells treated with combination of vemurafenib and telmisartan. Two-way ANOVA, ****P < 0.0001. (G) MitoTracker Red CMXRos staining for mitochondria in telmisartan-, vemurafenib- or the combination-treated A375 cells. Arrowheads point to the fragmented mitochondria. Scale bar 20 μm.