Fig. 5
Knockdown of ERRα inhibits tumor growth and promotes DDP sensitivity in EC organoids and a xenograft animal model. A Cell morphology of organoids at different magnifications was recorded using an optical microscope. Scale: 50, 100, and 500 µm. B The histological structure and morphology of EC organoids were verified using H&E staining. C Fraction of organoids of different sizes after treatment with DDP at different concentrations is shown. The amount of organoid debris following treatment with DDP at different concentrations increased, and the shape and size of the debris were recorded under a microscope. D Inhibitory effect of DDP (20 µM) and XCT790 (10 µM) alone or in combination with EC organoids was recorded using an optical microscope. The group treated with DMSO was used as the control group. Scale: 100 µm. E Evaluation of cell viability following treatment with DDP (20 µM) and XCT790 (10 µM) alone or in combination in each experimental group using the CellTiter-Glo assay. Cells treated with DMSO were used as the control group. F Representative images of the IHC of ERRα, NLRP3, and caspase-1 in EC organoids are shown (the values in each graph represent the average of three random fields per sample). The groups treated with DMSO and DDP alone were used as the control groups. G After pretreatment with or without XCT790 (10 µM), the IC50 of DDP in EC organoids was determined using the CCK8 assay. H Representative images of tumors captured at the end of the study and tumor size in BALB/c nude mice of the four treatment groups. I Tumor growth curves of the four treatment groups are shown. The KLE+DMSO and KLE+DDP treatment groups were used as control groups (day 0 was defined as the day when different cell groups were implanted). J Representative images of the IHC of ERRα, NLRP3, and GSDMD in tumor sections from xenograft mice are shown (each point represents the average of three random fields per sample). The KLE+DMSO and KLE+DDP treatment groups were used as control groups. K-L WB analysis of ERRα, NLRP3, caspase-1, GSDMD-N, IL-18, and IL-1β in tumor specimens of xenograft mice. Tubulin was used as a loading control. The KLE+DMSO and KLE+DDP treatment groups were used as control groups. Data are shown as the mean ± SD. Statistical tests: Student’s t-test. *p < 0.05; **p < 0.01; ***p < 0.001; ****p < 0.0001. Abbreviations: H&E, hematoxylin and eosin