The HIV reverse transcriptase Inhibitor Tenofovir suppressed DMH/HFD-induced colorectal cancer in Wistar rats

Colon rectal cancer (CRC) is the second commonest malignancy in developed countries and a significant cause of mortality. Tenofovir reportedly reduces the risk of hepatocellular carcinoma and interferes with cell cycle and cell proliferation. The current study investigated the potential antitumor effect of tenofovir against experimentally induced CRC. CRC was induced by 1,2-dimethylhydrazine (DMH, 20 mg/kg, once a week) and high-fat diet (HFD) in Wistar rats. Rats received tenofovir at a dose of 25 or 50 mg/kg (i.p.) for 24 weeks. Tenofovir-25 failed to significantly decrease the total number of dysplasia, adenoma and adenocarcinoma and to improve histopathological changes; however, tenofovir-50 resulted in no tumors seen in the colon lumen and a significant decrease in the total number of dysplasia and no adenoma or adenocarcinoma observed compared to DMH/HFD group. Tenofovir-25 failed to attenuate DMH/HFD-induced cell proliferation, whereas tenofovir-50 significantly decreased cell proliferation revealed by the decreased PCNA expression. Tenofovir-25 also failed to attenuate DMH/HFD-induced oxidative stress, whereas tenofovir-50 significantly attenuated oxidative stress as indicated by the decreased MDA concentration and SOD activity along with the increased GSH concentrations. Moreover, tenofovir-50 decreased Bcl-2 and cyclin D1 expressions in colon tissues compared with DMH/HFD group. Tenofovir-50 also significantly decreased INF-ɤ concentration in colon tissues. These findings suggest that the high dose of tenofovir (50 mg/kg) has antitumor potential against DMH/HFD-induced CRC, which might be mediated through the inhibition of cell proliferation, oxidative stress, and inflammation.