Figure 7.
Combination Therapy with Paclitaxel and the GLUT1 Inhibitor Synergistically Inhibits Endometrial Cancer Cell Progression (EMN24 Cells)
(A and B) Western blot analyses of spheroid cells after indicated ALDH modification (A) and after GLUT1 inhibition (B).
(C) Time course of the proliferation of the infected cells. n = 4 independent experiments, p < 0.01, Student's t test.
(D) Bright-phase images of the infected cells. Scale bars, 100 μm.
(E) Glucose uptake of spheroid cells of the infected cells. n = 4 independent experiments, p < 0.01, Student's t test.
(F and G) Relative cell viability (F) and glucose uptake (G) of spheroid cells after culture for 7 days with the indicated concentration of BAY876. n = 4 independent experiments, p < 0.01, Student's t test.
(H) Western blot analyses of spheroid cells after exposure to the indicated concentration of BAY876.
(I) Relative cell viability of spheroid cells after culture for 7 days with 2 nM paclitaxel. n = 4 independent experiments, p < 0.01, Student's t test.
(J) Relative cell viability of spheroid cells with the indicated concentrations of BAY876 and paclitaxel in vitro. Synergistic interaction was assessed with Combenefit software. n = 4 independent experiments.
(K) Volume (mean ± SEM) of xenograft tumors from 1 × 105 spheroid cells. Mice were separated into the vehicle (DMSO)-treated group, paclitaxel-treated group, BAY876-treated group, and paclitaxel + BAY876-treated group. n = 12 independent experiments, p < 0.001, Student's t test.
(L) Images of whole resected tumor xenografts excised on day 23. Scale bar, 10 mm.
(M) Representative immunostaining of GLUT1. Scale bars, 100 μm.
(N) Kaplan-Meier analyses of progression-free survival (upper) and overall survival (lower) in patients with advanced-stage ALDH-positive endometrial cancer. The patients were stratified into GLUT1-high (red lines, n = 7) and GLUT1-low (gray lines, n = 8) groups.
∗p < 0.05; ∗∗p < 0.01; ∗∗∗p < 0.001. See also Figure S4.