Figure 3. Lipid lowering agents decrease serum acetoacetate levels in xenograft mice and reduce VRAF V600E tumor growth.
(A) Tumor growth (left) and weight (right) of xenograft nude mice injected with human melanoma BRAF V600E-positive A375 cells (upper panels) that were orally treated with two different lipid lowering agents Niacin or Fluvastatin alone or in combination with intraperitoneal injection with acetoacetate (AA); Tumor growth (left) and weight (right) of xenograft nude mice injected with human melanoma BRAF V600E-positive A2058 (middle) cells or HMCB (NRAS Q61K; lower panels) cells that were orally treated with lipid lowering agent Fenofibrate alone or in combination with intraperitoneal injection with AA. Data are mean ± SEM for tumor growth and mean ± s.d. for tumor weight; p values were obtained by a two-way ANOVA test for tumor growth rates and a two-tailed Student’s t test for tumor masses.
(B–E) AA(B), 3HB (C), cholesterol (D), and triglyceride (E) levels in serum harvested from A375, A2058 and HMCB xenograft mice tissue. Data are mean ± s.d.; n=3; p values were obtained by a two-tailed Student’s t test.
(F–G) Western blot results show MEK1 and ERK1/2 phosphorylation (F) and BRAF-MEK1 binding (G) in tumor tissue samples obtained from xenograft mice tissue.
(H) Summarized results of IHC staining assay detecting Ki67-positive cells in tumor tissue samples from xenograft mice. Data are mean ± s.d.; n=3; p values were obtained by a two-tailed Student’s t test.
Also see Figures S4.