Anticancer Effect of in Vivo Inhibition of Nitric Oxide Synthase in a Rat Model of Breast Cancer

Autor: Nikolay Avtandilyan, Hayarpi Javrushyan, Mikayel Ginovyan, Anna Karapetyan, Armen Trchounian
Rok vydání: 2021
DOI: 10.21203/rs.3.rs-1180489/v1
Popis: High expression of nitric oxide (NO)-synthase has been found in different cancers like cervical, breast, and central nervous system. NO-synthase activity inhibition has been suggested as a possible tool to prevent breast cancer. The anti-tumor therapeutic effect of L-nitro arginine methyl ester (L-NAME) in vivo remains understudied. Here we hypothesized that NOS inhibition by L-NAME has some antitumor effects on breast cancer development as it inhibits NO levels, which is a pathophysiological modulator of cell proliferation, cell cycle arrest, apoptosis, and angiogenesis. We utilized a novel anti-cancer treatment model by the administration of NO-synthase inhibitor L-NAME (30 mg/kg in a day, intraperitoneal), injected every third day for five weeks (in parallel to tumors evolution) in opposition to high activity of NOS during 7,12-dimethylbenz[a]anthracene-induced breast tumor in rats in vivo. The blood concentrations of nitrite anions, polyamines, malondialdehyde, NH4+ levels, and arginase activity decreased in DMBA+L-NAME-treated rats compared with DMBA rats. The reduction of these compounds also affects the decrease of the mortality rate of rats, tumor number, weight and volume, and the histopathological grade of breast cancer. Treatment with L-NAME showed increases in time of tumor incidence and body weight compared with DMBA-cancer rats. Therefore, the co-administration of L-NAME influences as a potent anti-cancer agent to treat breast cancer and can lead to the development of therapeutic methods for cancers in the future.
Databáze: OpenAIRE