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. 2023 Aug 18;4(9):101162. doi: 10.1016/j.xcrm.2023.101162

Figure 5.

Figure 5

The GLUT1/ALDOB/G6PD axis contributes to drug resistance

(A) Heatmap showing the relative abundance of nucleoside and nucleoside derivatives in glucomet-PDAC (n = 15) and lipomet-PDAC (n = 13).

(B) Heatmap showing Pearson correlation coefficients between the RNA expression levels of ALDOB/GLUT1 and nucleoside derivatives.

(C and D) DAC-18 (lipomet) and DAC-42 (glucomet) organoids were treated with 5-FU alone or in combination with pyrimidine nucleosides (uridine, cytidine, and thymidine, 240 μM) for 5 days, and cell viability was determined by CellTiter-Glo assays.

(E and F) DAC-18 (lipomet) and DAC-42 (glucomet) organoids were treated with PTX alone or in combination with pyrimidine nucleosides (240 μM) for 5 days, and cell viability was determined by CellTiter-Glo assays.

(G) Effect of GLUT1 knockdown on 5-FU responsiveness of DAC-34 (glucomet) as determined by CellTiter-Glo assays 120 h after treatment with 5-FU.

(H) Effect of ALDOB overexpression on the 5-FU responsiveness of DAC-42 (glucomet) as determined by CellTiter-Glo assays 120 h after treatment with 5-FU.

(I) Effect of G6PD knockdown on the 5-FU responsiveness of DAC-42 (glucomet) as determined by CellTiter-Glo assays 120 h after treatment with 5-FU.

(J) Effect of ALDOB overexpression on 5-FU responsiveness in the DAC-42 (glucomet) ODX model (n = 6 per group).

(K) Effect of pyrimidine nucleotide (240 μM) on 5-FU sensitivity in control and GLUT1 knockdown organoids by CellTiter-Glo assays at 120 h posttreatment.

(L) Effect of pyrimidine nucleotide (240 μM) on 5-FU sensitivity in control and ALDOB overexpression organoids by CellTiter-Glo assays at 120 h posttreatment.

(M) Effect of R5P (1 mM) on 5-FU sensitivity in control and GLUT1 knockdown organoids by CellTiter-Glo assays at 120 h posttreatment.

(N) Effect of R5P (1 mM) on 5-FU sensitivity in control and ALDOB-overexpressing organoids by CellTiter-Glo assays at 120 h posttreatment.

(O) Effect of R5P (1 mM) on 5-FU sensitivity in control and G6PD knockdown organoids by CellTiter-Glo assays at 120 h posttreatment.

(P and Q) Effect of purine nucleotides (guanosine and adenosine, 200 μM) on 5-FU and GEM sensitivity in control and GLUT1 knockdown organoids by CellTiter-Glo assays at 120 h posttreatment.

All dose-responsive curves were performed with 3 technical replicates. Data are presented as the mean values ± SEMs, and statistical significance was computed by unpaired Student’s t test (∗p < 0.05; ∗∗p < 0.01; ∗∗∗p < 0.001) (C–Q).