Fig. 3: KLF6 cooperated with FOSL2 to maintain the 5-FR resistance of HCT15-FR cells.

a The IC₅₀ values of FOSL2, KLF6, FOSL2 and KLF6 in HCT15-FR cells, FOSL2- and KLF6-knockdown HCT15-FR cells, and FOSL2- and KLF6-overexpressing HCT15-Pa cells were calculated after 5-FU administration. These findings demonstrated that FOSL2 and KLF6 are essential for maintaining 5-FU resistance in a synergistic manner. b HCT15-FR cells, HCT15-FR cells with FOSL2 knockdown, KLF6 knockdown, FOSL2 and KLF6 knockdown, HCT15-Pa cells, and HCT15-Pa cells with FOSL2 overexpression, KLF6 overexpression, and FOSL2 and KLF6 overexpression were cultured in six-well plates with 5-FU administration. The results showed that FOSL2 cooperated with KLF6 to increase the viability of HCT15-FR cells. c An EdU assay was used to examine the viability of HCT15-FR cells and HCT15-Pa cells after transfection and treatment with 5-FU. These results indicated that FOSL2 cooperated with KLF6 to increase the percentage of EdU-positive HCT15-FR cells. d A flow cytometry apoptosis assay was performed to examine the apoptosis rates of HCT15-FR cells and HCT15-Pa cells after transfection and treatment with 5-FU. HCT15-Pa and HCT15-FR cells were incubated with fluorescein-isothiocyanate-conjugated annexin V and propidium iodide followed by incubation in the dark at room temperature for 30 min. The results revealed that FOSL2 cooperated with KLF6 to decrease the apoptosis rates of HCT15-FR cells. e Subcutaneous tumors formed from HCT15-FR cells, HCT15-FR cells with FOSL2 knockdown, KLF6 knockdown, and FOSL2 and KLF6 knockdown. The tumor volume was measured every 3 days after injection. The tumor weights of the subcutaneous xenografts are shown. These results suggest that FOSL2 cooperated with KLF6 to maintain 5-FU resistance in a synergistic manner.