Title: Chemopreventive and anticancer activities of indomethacin and vitamin D combination on colorectal cancer induced by 1,2‑dimethylhydrazine in rats
Abstract: Several studies have revealed that the combination of indomethacin, a nonsteroidal anti‑inflammatory drug (NSAID), and vitamin D reduces the risk of common types of cancers. Nonetheless, research on the deal concentrations used to test the impact of vitamin D on colon cancer is deficient. Along these lines, the aim of the present study was to evaluate the possible role of indomethacin and vitamin D as a preventative as well as a therapeutic operator for colon cancer growth induced by dimethylhydrazine (DMH) in male Albino rats. Fifty male albino rats were utilized in this examination; five groups were assigned from the animals (10 animals each): i) control group considered healthy animals; ii) carcinogen group that received DMH only; iii) prophylactic group; iv) vitamin D and indomethacin‑treated group; and v) 5‑flurouracil (5‑FU) group. Western blot technique was used to determine the expression of carcinoembryonic antigen (CEA) and platelet‑derived growth factor (PDGF). Overexpression of CEA and PDGF was noted in the carcinogenic group, while expression of CEA and PDGF in the prophylactic, vitamin D and indomethacin and 5‑FU groups were markedly reduced. There was a likewise decline in tissue caspase‑3 activity and antioxidant parameters in the carcinogenic group, while, there was an increase in these markers in the 5‑FU group as well as the prophylactic and vitamin D and indomethacin groups. The combination of vitamin D and indomethacin markedly reduced the incidence and severity of colon cancer. The molecular, biochemical and histopathological analysis related with the oral administration of vitamin D and indomethacin display its capacity to limit the frequency of colorectal cancer.