The effect of Arginine on gastric cancer cell behaviour : molecular mechanisms of action

The effect of arginine on gastric cancer cell behaviour: Molecular mechanisms of action – Abstract of thesis In gastric cancer patients undergoing surgical resection, the immunosuppression associated with surgery together with the malnutrition, which these patients often have, contribute substantially to a 40% risk of major peri-operative morbidity. Standard nutritional support in these patients has had mixed results. However, the ingestion of key nutrients, which modulate immune, inflammatory and metabolic pathways, also known as immunonutrition, offers a therapeutic modality, by reducing infectious complications by approximately 50%. However, studies have shown that arginine a key nutrient included in immunonutritional regimens not only has immune-enhancing effects but also has the ability to both stimulate and inhibit tumour growth. Therefore concerns remain with regard to the peri-operative use of arginine with regard to tumour growth and dissemination around the time of surgery. The aims of this study were to evaluate the in vitro effects of arginine on gastric cancer cell growth and invasion and the potential molecular mechanisms underlying any changes. A feasibility study was conducted to evaluate the influence of immunonutrition on gastric cancer patients by way of effect on expression of genes involved with tumour growth and invasion. The in vitro data confirmed that both stimulation of apoptosis associated with an increase in caspase 8 expression and cell cycle arrest at G2 phase independent of the effects of both p21 and p53 were associated with inhibition of AGS cell growth. No significant effect on invasion was demonstrated on AGS cells treated with arginine. The feasibility study demonstrated the challenges associated with extracting adequate quantity and quality of RNA from gastric tumour tissue. However, a total of 668 genes demonstrating a two fold change in gene expression were identified in the gastric tumour biopsies following feeding with immunonutrition. In summary, our data confirms inhibition of gastric cancer cell growth with arginine supplementation. However, the peri-operative use of arginine enriched nutritional support in patients with gastric cancer requires further assessment.EThOS - Electronic Theses Online ServiceGBUnited Kingdo