Creatine supplementation does not promote tumor growth or enhance tumor aggressiveness in Walker-256 tumor-bearing rats

Abstract Aim. To analyze the effect of creatine (Cr) supplementation on tumor microenvironment, evaluating parameters of tumor aggressiveness. Methods. Sixteen male Wistar rats were randomly assigned in 2 groups (n=8/group): tumor-bearing (T) and tumor-bearing supplemented with Cr (TCr). Cr supplementation was provided in drinking-water for a total of 21 days. After 11 days of creatine supplementation (TCr group) or water (T group), Walker-256 tumor cells were inoculated subcutaneously at the right flank of all rats, which keep receiving Cr supplementation (TCr group) or water (T group) for more 10 days. Total period of experiment was 21-days. Results. Tumor weight corresponded to approximately 3.5±0.9% of animal body weight in T group; Cr supplementation did not accelerate tumor growth and did not increase tumor size. The histopathological analysis demonstrated presence of nuclear pleomorphisms and atypical nuclei, with the presence of low-differentiated tumor cells, in both groups. Cr supplementation did not alter apoptosis and cell proliferation markers as well as tumor capsule thickness and viable tumor area. Conclusion. Cr supplementation in Walker-256 tumor-bearing rats did not induce significant changes in the tumor development, as well as did not interfere with parameters of tumor aggressiveness, such as the level of cell differentiation and proliferation.