SIRT1 silencing as modulator of oxaliplatin effects in colon cancer cells

Abstract

[eng] The sirtuin protein family has emerged as important regulators of diverse pathological events, including life-span extension, age-related disorders, inflammation and cancer. sirtuin 1 (SIRT1) protein is the most extensively studied member of this family. SIRT1 can deacetylate histones and also nonhistone substrates involved in multiple signaling pathways in cancer. Some studies have suggested that SIRT1 can act both as a tumor suppressor or tumor activator, depending on its target and specific pathway. On the one hand, SIRT1 help to protect DNA from damage and oxidative stress, maintaining genomic stability and protecting against cancer. In the other hand, its known to play a role in inflammation, thus promoting cell division under stress conditions, what can be associated with tumorigenesis. Although molecular mechanisms are not well understood in colorectal cancer, SIRT1 is also associated with epithelial-to-mesenchymal transition (EMT), which is important for the development of cancer metastasis. Some studies have shown that SIRT1 overexpression correlates with a worse survival, promoting migration and invasion, while Sirt1 silencing represses the malignant behavior of cancer cells. The aim of the present study is to evaluate the effect of silencing SIRT1 in colorectal carcinoma cells (SW620 cell line) combined with the cytotoxic agent Oxaliplatin, in terms of inflammation and EMT.