Figure 7.

LPC(24:1) secretion is specifically up-regulated upon 16:4(n-3) stimulation of splenic macrophages. A) LPC analysis of sCM from wild-type mice that were incubated with 16:4(n-3) revealed 3 significantly up-regulated unsaturated LPCs compared with vehicle control–incubated splenic macrophages. LPC(24:1) up-regulation in wild-type sCM was lost in GPR120^−/− sCM. In addition, LPC(24:1) was also lost when splenocytes were incubated with 16:4(n-3) in the presence of the PLA₂ inhibitor AACOCF₃. B) Coadministration of cisplatin (cis) and 10 nmol LPC(24:1) was sufficient to induce chemotherapy resistance, whereas coadministration of cisplatin and 10 nmol of LPC(24:0) could not. C) Tumors of mice that were treated with cisplatin and LPC(24:1) had levels of γH2AX similar to control mice, whereas mice that were treated with cisplatin alone or cisplatin and LPC(24:0) showed increased levels of γH2AX compared with control mice. Analysis of γH2AX was performed 4 h post-treatment. Scale bars, 50 μm. Experiments in Panels B and C were conducted in C26 tumor-bearing BALB/c mice. All graphs show combined results of 2 independent experiments with similar outcomes (A: n = 4 per group; B: n = 8 per group; C: n = 8 per group). AUC, area under the curve; ns, not significant. Data are presented as means ± sem. Statistical significance was determined by 1-way ANOVA (B, C) or 2-tailed Student’s t test (A, D); all compared to cisplatin alone unless indicated otherwise. *P < 0.05; **P < 0.01.