Inhibition of FXa could be a novel therapeutic target associated with hypoxia-associated tumor behavior?

Figures

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  Fig. 1. Visualization of Protein–Ligand and Protein–Protein Interactions. Involving Rivaroxaban, FXa, and HIF1α. a, b 3D and 2D molecular interactions of Rivaroxaban at the active site of FXa (purple: FXa; brown: Rivaroxaban). c, d 3D and 2D molecular nteractions of rivaroxaban at the active site of HIF1α (purple: HIF1α; brown: rivaroxaban). e Structural depiction of the FXa–HIF1α interaction (FXa in purple; HIF1α in brown). f Interacting residues at the FXa (Chain A)–HIF1α (Chain B) protein–protein interface

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  Fig. 2. Cell viability in colorectal cell lines in both normoxic and hypoxic conditions. Data represents the mean ± SEM of three independent experiments. Statistical differences were analyzed with the One-Way ANOVA test (* indicates p < 0.05)

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  Fig. 3. Colony forming abilities of HCT-116 and HT-29 cell lines were examined Rivaroxaban in hypoxic conditions. a Examination of colony formation in both cell lines with non-toxic rivaroxaban doses in hypoxic conditions (H 101 nM and H 105 nM). b Relative number of migrating cells measured by Image J. Data represent the mean ± SEM of three independent experiments. Statistical differences were analyzed by Two-Way ANOVA test (ns indicates not significance, * indicates p < 0.05, *** indicates p < 0.0001, **** indicates p < 0.00001)

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  Fig. 4. Rivaroxaban inhibited the migrative properties of a HCT-116 and b HT-29 cell lines under hypoxic conditions. Migration inhibition of HCT-116 (a) and HT-29 (b) with the treatment of non-toxic doses (101 nM and 105 nM) of Rivaroxaban for 0 and 48-h. c The wound widths were quantified in lower panels. Data represents the mean ± SEM of three independent experiments. Statistical differences were analyzed with Two-Way ANOVA test (ns indicates not significance, and *** indicates p < 0.0001)

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  Fig. 5. The migratory properties of HCT-116 and HT-29 cell lines were treated with Rivaroxaban in hypoxic conditions. Inhibition of migration in both cell lines by non-toxic rivaroxaban doses in hypoxic conditions (H 101 nM and H 105 nM). a Transwell cell migration assay. b Relative number of migrating cells measured by Image J. Data represent the mean ± SEM of three independent experiments. The Two-Way ANOVA test analyzed statistical differences (* indicates p < 0.05)

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  Fig. 6. Immunofluorescent staining images and bar graphs. a HCT-116, b HT-29. c Bar graphs. The cell lines (indicated on the top of the panels) were treated with 101 nM and 105 nM rivaroxaban, shown as immunofluorescence detection of E-cadherin, N-cadherin, HIF-1α, and GLUT-1. (and indicates not significance, * indicates p < 0.05)