Therapeutic Effect Of Sodium Selenite On H22 Hepatocarcinoma Ascites Model And Its Se Nps Conversion

Intraperitoneal chemotherapy is currently the main method for the treatment of malignant tumors in the abdominal cavity and implanted metastases in the abdominal cavity.Sodium selenite is an inorganic form of selenium with a +4 valence and oxidation-reduction activity.Once sodium selenite access to organisms,it can be metabolized by the thioredoxin system(Trx)and glutathione reduced(Grx)coupled glutathione(GSH)system to generate a large amount of reactive oxygen species(ROS).The Trx system and the Grx-coupled GSH system are highly expressed in cancer cells.Some in vivo experiments have demonstrated that intraperitoneal injection of sodium selenite has a powerful therapeutic effect against several lines of cancer cells inoculated in the abdominal cavity without noticeable host toxic reactions.However,intracellular selenium forms responsible for exerting anticancer function of selenite remain obscure.The present study aimed at delineating the mechanism of intraperitoneal chemotherapy,the potential energy of sodium selenite,and the major selenium form under such a condition.Furthermore,this study may added anti-cancer background of sodium selenite and provide a new idea for the drug selection of intraperitoneal chemotherapy.Hepatocarcinoma 22(H22)ascites mice model is a stable and controllable intraabdominal high-malignant tumor model in our laboratory.By inoculating 20 million of H22 hepatocarcinoma cells in the abdominal cavity of male Kunming mice,after 2 days of living culture,the cancer cells grew to a stable 200 million,and the total extracellular glutathione peroxidase(GPx),glutathione reductase(GR),and glutathione transferase(GST)activity in the abdominal cavity increased correspondingly.Based on this model,sodium selenite shows a strong anti-cancer effect.The maximum tolerated dose of sodium selenite is stronger than the clinically broad-spectrum anticancer drug cisplatin,which causes changes in the morphology of cancer cells,stagnation of growth cycle,and massive degradation of proteins.A large number of reactive oxygen species are produced and the number of H22 cell is greatly reduced.Finally,the survival time and survival rate of mice are prolonged.Behind the powerful anti-cancer effect,qualitative and quantitative analyses revealed that selenium nanoparticles(SeNPs)accounted for approximate 70% selenium in H22 cells post selenite administration as short as 10 minutes and remained stable thereafter.And selenium accumulates less in normal tissues,and SeNPs cannot be detected.We have demonstrated in vitro that sodium selenite is metabolized into SeNPs under the action of the Trx system and the Grx-coupled GSH system and generates a large amount of reactive oxygen species.Moreover,the metabolism of SeNPs is also carried out by two major systems and also generates a large amount of reactive oxygen species.Therefore,this paper proves that sodium selenite is the prodrug of SeNPs.In the presence of a large number of proteins in the body,selenite is metabolized into selenium atoms and rapidly encapsulated by proteins to form SeNPs and continue to exert anti-cancer effects.