Figure 4. Effects of fisetin, sorafenib and their combination on tumor growth of subcutaneously implanted BRAF-mutated melanoma cells in athymic nude mice.

Athymic (nu/nu) female nude mice were subcutaneously injected with A. A375 cells B. SK-MEL-28 cells in each flank of mouse to initiate tumor growth. Mice were then randomly divided into four groups with 6 mice in each group. Twenty-four hours after cells implantation, mice were treated with fisetin, sorafenib and their combination as described in materials and methods section. Values represent mean ± SEM. *p < 0.05, **p < 0.01 and ***p < 0.001 versus control group. ^@p < 0.05, ^@@p < 0.01 and ^@@@p < 0.001 versus fisetin treated group. ^$p < 0.05, ^$$p < 0.01 and ^$$$p < 0.001 versus sorafenib treated group. Similarly, in another set of experiments C. & D., mice were randomly divided into four groups with 6 mice in each group when their tumor size reached approximately 200 mm³. Mice were treated with test agents as described in materials and methods section. All mice were sacrificed when tumors reached a volume of ∼1200 mm³ in the control group. Average tumor volume of the control and treated groups was plotted over days after tumor cell inoculation. Values represent mean ± SEM. *p < 0.05, **p < 0.01 versus control group. ^@p < 0.05 versus fisetin treated group. ^$p < 0.05 versus sorafenib treated group.