Introduction
Cancer cells are known to exhibit metabolic adaptations in hypoxic environments. It is believed that transcription factors that are members of the HIF family are the key to this adaptability. Although metabolic adaptability keeps cancer cells alive, it also gives them an aggressive phenotype and reduces the effectiveness of treatments. In this work, we used a oral cavity cancer cell-line that is known to be resistant to a hypoxic microenvironment in an effort to contribute to new treatment approaches. Material and Methods

In order to investigate the effects of rivaroxaban on the UPCI-SCC-131 Oral Cavity cancer cell line under normoxic and hypoxic conditions, this study used viability analysis, wound healing experiments, and immunofluorescence to measure the expression levels of HIF-1 alpha, GLUT-1, and LDHA. A method of chemical hypoxia using sodium sulfite, which had been optimised in our previous studies, was used to create the hypoxic conditions.

Results and Discussions

Cell viability decreased in the hypoxic condition compared to the normoxic condition as the rivaroxaban concentration increased. In parallel, when analysing wound healing results, it was observed that wound opening did not change in the hypoxic group, whereas wound closure occurred in the normoxic group. Furthermore, immunofluorescence staining results showed that E-cadherin, LDH-A, HIF-1 alpha and GLUT-1 expression levels, which were observed to increase in hypoxia compared to normoxia, decreased after rivaroxaban treatment in hypoxia.
Conclusion
The suppression of HIF-1 alpha, which is essential for enhanced metabolic adaptability in hypoxic environments, was found to produce positive feedback loops in cell behaviour, as per our data. The augmentation of pro-coagulant activity in the tumor microenvironment was assumed to be caused by rivaroxaban, an inhibitor of FXa, which inhibits HIF-1 alpha. In the hypoxic tumor microenvironment, rivaroxaban might be a novel target in this situation.

O.B. was supported by TUBITAK 2211C Domestic Priority Doctoral Scholarship Program, and Council of Higher Education 100/2000 scholarship in priority field program. The study is funded by Dokuz Eylul University Scientific Research Projects Coordination Unit with project number TSG20222576.