Figure 7.

Dietary Supplementation of Arachidonic Acid Reverses the Sensitivity of PIK3CA Mutant Tumors to cPLA2 Inhibition

(A) Schematic of in vivo experimental design and profiling of breast cancer cell line xenografts with REIMS.

(B and C) Relative tumor growth of CAL-51 (PIK3CA MUT)-derived xenografts stably expressing control shGFP or two independent shRNAs targeting cPLA2 (cPLA2-sh1 and cPLA2-sh5) under (B) fat-free or (C) “Western” diets.

(D) Weights of tumors excised at the end of the experiments (B) and (C).

(E and F) Relative tumor growth of Hs578T (PIK3CA WT)-derived xenografts stably expressing control shGFP or two independent shRNAs targeting cPLA2 under (E) fat-free or (F) “Western” diets.

(G) Weights of tumors excised at the end of the experiments (E) and (F).

(H) Representative images of H&E staining from resected tumors in (D) and (G). The black masks in (H) represent viable tumor area, while unshaded regions correspond to necrotic tissue.

(I and J) Quantification of viable tumor area from (I) PIK3CA MUT (CAL-51) and (J) PIK3CA WT (Hs578T) tumor sections based on the analysis depicted in (H).

(K and L) AA levels measured by REIMS in (K) PIK3CA MUT (CAL-51) and (L) PIK3CA WT (Hs578T) snap frozen excised tumors. AA intensities are reported as scaled values to the appropriate shGFP-fat-free diet condition. Data in (B), (C), (E), (F), (K), and (L) represent the mean ± SEM of relative tumor growth or tumor REIMS measurements from n = 3–5 mice. n.s., not significant; ^∗p < 0.05; ^∗∗p < 0.01; ^∗∗∗p < 0.001; p values in (B), (C), (E), and (F) were calculated using two-way ANOVA, and one-way ANOVA followed by unpaired, two-tailed Student’s t test with Bonferroni correction was used in (D), (G), and (I)–(L).