Chemotherapy with Cis and DOX causes anorexia and selective activation of the IRE1α-XBP1 pathway in the liver. Related to Fig. 1. (A and B) Food intake (A) and body weight changes (B) of C57BL/6 mice treated with one dose of Vehicle (i.p.), DOX (10 mg per kg body weight, i.p.), Cis (10 mg per kg body weight, i.p.) or PTX (10 mg per kg body weight, i.p.) at 1 day. Vehicle, n = 5; DOX, n = 7; Cis, n = 7; PTX, n = 7. (C) Top 10 enriched HALLMARK pathways by the GSEA that are differentially regulated between liver samples from Vehicle- and Cis-treated mice. HALLMARK pathways are defined using the FPKM values of all the detected genes in livers from Cis-treated mice, and ranked according to the NES. (D) GSEA showing DOX-induced enrichment of the “unfolded protein response” gene signature in the liver (NES = 2.37 and FDR q-value < 0.001). The solid bars represent individual genes in the “unfolded protein response” gene set. (E) GSEA showing Cis-induced enrichment of the “unfolded protein response” gene signature in the liver (NES = 1.66 and FDR q-value = 0.006). The solid bars represent individual genes in “unfolded protein response” gene set. (F) Venn diagram showing the upregulated genes (compared to Vehicle treatment) that overlapped in liver samples from DOX- and Cis-treated mice. (G and H) GO analysis of the 135 overlapping genes in F. (G) Bubble plot of the top six enriched pathways by GO Term Biological Process analysis. (H) Bubble plot of the top six enriched pathways by GO Term Cellular Component analysis. The diameter of the circle is proportional to the number of DEGs enriched in the indicated pathways. The color of the circle represents the value of −Log10(P value). (I) The top 10 enriched pathways from GO Biological Process analysis by GSEA based on differentially regulated genes in the liver between Vehicle- and DOX-treated mice. The enriched pathways are defined using the FPKM values of all the detected genes in livers from DOX-treated mice, and ranked according to the NES. (J) The top four enriched motifs according to the MOTIF analysis by GSEA of the liver from Vehicle- and DOX-treated mice. The enriched motifs are defined using the FPKM values of all the detected genes in liver samples from DOX-treated mice and ranked according to the NES. (K) GSEA showing the enrichment of “XBP1” target gene signatures in liver samples from DOX-treated mice (NES = 1.66 and FDR q-value = 0.034). The solid bars represent individual genes in the “XBP1” gene set. (L) Western blot analysis of the indicated proteins in liver lysates from 8-wk-old mice treated with a single dose of DOX (10 mg per kg body weight, i.p.). Liver samples were collected 1 day after injection. Each sample represents an individual animal. (M) Western blot analysis of the indicated proteins in liver lysates from 8-wk-old mice treated with a single dose of Cis (10 mg per kg body weight, i.p.). Liver samples were collected 1 day after injection. Each sample represents an individual animal. Data are representative of two independent experiments and presented as mean ± SEM. ***P < 0.001 (DOX versus Vehicle), ###P < 0.001 (Cis versus Vehicle) by unpaired two-tailed Student’s t test. Source data are available for this figure: SourceData FS1.
Figure S1.

Chemotherapy with Cis and DOX causes anorexia and selective activation of the IRE1α-XBP1 pathway in the liver. Related to Fig. 1. (A and B) Food intake (A) and body weight changes (B) of C57BL/6 mice treated with one dose of Vehicle (i.p.), DOX (10 mg per kg body weight, i.p.), Cis (10 mg per kg body weight, i.p.) or PTX (10 mg per kg body weight, i.p.) at 1 day. Vehicle, n = 5; DOX, n = 7; Cis, n = 7; PTX, n = 7. (C) Top 10 enriched HALLMARK pathways by the GSEA that are differentially regulated between liver samples from Vehicle- and Cis-treated mice. HALLMARK pathways are defined using the FPKM values of all the detected genes in livers from Cis-treated mice, and ranked according to the NES. (D) GSEA showing DOX-induced enrichment of the “unfolded protein response” gene signature in the liver (NES = 2.37 and FDR q-value < 0.001). The solid bars represent individual genes in the “unfolded protein response” gene set. (E) GSEA showing Cis-induced enrichment of the “unfolded protein response” gene signature in the liver (NES = 1.66 and FDR q-value = 0.006). The solid bars represent individual genes in “unfolded protein response” gene set. (F) Venn diagram showing the upregulated genes (compared to Vehicle treatment) that overlapped in liver samples from DOX- and Cis-treated mice. (G and H) GO analysis of the 135 overlapping genes in F. (G) Bubble plot of the top six enriched pathways by GO Term Biological Process analysis. (H) Bubble plot of the top six enriched pathways by GO Term Cellular Component analysis. The diameter of the circle is proportional to the number of DEGs enriched in the indicated pathways. The color of the circle represents the value of −Log10(P value). (I) The top 10 enriched pathways from GO Biological Process analysis by GSEA based on differentially regulated genes in the liver between Vehicle- and DOX-treated mice. The enriched pathways are defined using the FPKM values of all the detected genes in livers from DOX-treated mice, and ranked according to the NES. (J) The top four enriched motifs according to the MOTIF analysis by GSEA of the liver from Vehicle- and DOX-treated mice. The enriched motifs are defined using the FPKM values of all the detected genes in liver samples from DOX-treated mice and ranked according to the NES. (K) GSEA showing the enrichment of “XBP1” target gene signatures in liver samples from DOX-treated mice (NES = 1.66 and FDR q-value = 0.034). The solid bars represent individual genes in the “XBP1” gene set. (L) Western blot analysis of the indicated proteins in liver lysates from 8-wk-old mice treated with a single dose of DOX (10 mg per kg body weight, i.p.). Liver samples were collected 1 day after injection. Each sample represents an individual animal. (M) Western blot analysis of the indicated proteins in liver lysates from 8-wk-old mice treated with a single dose of Cis (10 mg per kg body weight, i.p.). Liver samples were collected 1 day after injection. Each sample represents an individual animal. Data are representative of two independent experiments and presented as mean ± SEM. ***P < 0.001 (DOX versus Vehicle), ###P < 0.001 (Cis versus Vehicle) by unpaired two-tailed Student’s t test. Source data are available for this figure: SourceData FS1.

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