Fig. 6

Both HIF1A knock-down and pharmacological inhibition of HIF-1α are effective for reducing 5-FU resistance in vivo. a-e Effect of HIF1A knockout on 5-FU resistance in subcutaneously-implanted WT or 5-FU-R cells in a nude mouse model. One week after subcutaneous injection, the mice were treated intraperitoneally with 25 mg/kg 5-FU or saline three times a week. Tumors were harvested when the diameter was > 1.5 cm (a). Tumor volumes were quantified by V = L × W²/2 (where L is the length and W is the width) (b, c). Representative images of IHC staining for Ki-67, scale bar = 200 μm (d). Percentage of Ki-67-positive cells (e). f-i Effect of IDF-11774 on 5-FU resistance in subcutaneously-implanted WT or 5-FU-R cells in a nude mouse model. Tumors harvested from subcutaneously-implanted nude mice treated with saline (control), 5-FU alone (25 mg/kg, three times a week), IDF-11774 alone (30 mg/kg, twice a week) or 5-FU together with IDF-11774 (f). Tumor volumes were quantified by V = L × W²/2 (where L is the length and W is the width) (g, h). Percentage of Ki-67-positive cells (i). j-m Effect of IDF-11774 on 5-FU resistance in a PDXs NOD/scid mouse model. Tumors harvested from subcutaneously-implanted nude mice treated with saline (control), 5-FU alone (25 mg/kg, three times a week), IDF-11774 alone (30 mg/kg, twice a week) or 5-FU together with IDF-11774 (j). Tumor volumes were quantified by V = L × W²/2 (where L is the length and W is the width) (k, l). Percentage of Ki-67-positive cells (m). Data are presented as means ± SEM. Bar chart data were compared by ANOVA (* p < 0.05, ** p < 0.01, and *** p < 0.001)