Rivaroxaban ­an anticoagulant agent­ appears to have a role in reversing the hypoxia­ induced metabolic adaptation observed in colorectal cancer cell lines

The pro­coagulant activity of cancer is known for its ability to induce FXa and thrombin. FXa promotes cancer growth and metastasis via PAR, according to recent literature reports. This study aimed to investigate the effect of the inhibition of FXa, which is known to play a crucial role in cancer metabolism in hypoxia, on the behaviour of colon cancer cell lines HCT­116 and HT­29. We performed studies under both normoxic and hypoxic conditions. We used immunofluorescence to assess the expression of key elements in tumor metabolism, including HIF­1 alpha, LDH­A and GLUT­1, following administration of rivaroxaban, an FXa inhibitor known to not affect cell viability. The expression of HIF­1 and LDH­A increased under hypoxia. However, it was observed that the expression decreased in the rivaroxaban­ treated group. Strikingly, no statistically significant difference was found for GLUT­1 expression. Furthermore, in the analysis of E­cadherin and N­cadherin expression levels, the effect of rivaroxaban on migration under hypoxia was statistically significant in comparison to the control group. These findings were further supported by the statistical results of the wound patency in the wound healing experiment. Based on the results of this study, we demonstrate that the inhibition of FXa with rivaroxaban may represent a novel target for the treatment of tumor hypoxia. (O.B. supported by the CoHE 100/2000 project. The study is funded by Dokuz Eylul University Scientific Research Projects Coordination Unit with project number TSG­2022­2576).