Combination Therapy with Paclitaxel and the ALDH Inhibitor Synergistically Inhibits Endometrial Cancer Cell Progression (EMN24 Cells)
(A) Responses of ALDH-high and ALDH-low cells to different concentrations of cisplatin and paclitaxel after treatment for 7 days. n = 4 independent experiments, Student's t test.
(B) FACS analyses of ALDH activity in ALDH-high cells in the presence or absence of paclitaxel or cisplatin after in vitro treatment for 7 days.
(C) Western blot analyses of ALDH-high cells treated with paclitaxel for 7 days.
(D) Correlation between ALDH activity and paclitaxel half-maximal inhibitory concentration (nM).
(E) Bright-phase images of spheroids after in vitro paclitaxel and disulfiram treatment for 7 days. Scale bars, 100 μm.
(F) Relative cell viability of spheroid cells after culture for 7 days with the indicated concentrations of ALDH inhibitor and paclitaxel. Synergistic interaction was assessed with Combenefit software. n = 4 independent experiments.
(G) In vitro limiting dilution analysis over 14 days culture using spheroid cells exposed to 7 days treatment of disulfiram and/or paclitaxel in vitro.
(H) Volume (mean ± SEM) of xenograft tumors from 1 × 105 spheroid cells. Mice were separated into the vehicle (DMSO)-treated group, paclitaxel-treated group, and paclitaxel + disulfiram-treated group. n = 8 independent experiments, p < 0.001, Student's t test.
(I) Images of whole resected tumor xenografts excised on day 23. Scale bar, 10 mm.
(J) ALDH activity in cancer cells derived from xenograft tumors.
∗p < 0.05; ∗∗p < 0.01; ∗∗∗p < 0.001. See also Figure S3.