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. Author manuscript; available in PMC: 2018 Feb 7.
Published in final edited form as: Cell Metab. 2017 Jan 12;25(2):358–373. doi: 10.1016/j.cmet.2016.12.010

Figure 3. Lipid lowering agents decrease serum acetoacetate levels in xenograft mice and reduce VRAF V600E tumor growth.

Figure 3

(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.