Pathophysiological link between diabetes and colorectal cancer: effect of diabetic microenvironment, metformin and 5-fluorouracil on glyoxalase 1 protein level
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| Year of publication | 2018 |
| Type | Conference abstract |
| Citation | |
| Description | Epidemiologic studies showed that (i) type 2 diabetes mellitus is associated with increased risk of certain cancers including colorectal cancer (CRC) and that (ii) CRC clinical outcome is worse in diabetics compared to non-diabetic subjects. On the other hand, antidiabetic treatment, specifically metformin, was associated with better prognosis and also increased efficacy of standard chemotherapeutic agents in CRC. Despite the indirect evidence of anticancer effects of metformin and sporadic evidence of its benefit as an adjuvant to standard chemotherapy mechanisms are not fully understood yet. One of links explaining adverse role of diabetes in cancer incidence and outcomes might involve increased dicarbonyl stress with subsequent up-regulation of glyoxalase 1 (GLO1). While increased GLO1 level or activity in diabetic patients may be beneficial, in some tumors, including CRC, a higher level of GLO1 may confer invasive, metastatic potential and diminish tumor sensitivity to therapy. So far it is unclear whether metformin might play a direct role in regulating cancer sensitivity to therapy and whether GLO1 might mediate such effects. Aim of the project was to study the effect of (i) diabetic microenvironment, (ii) metformin and (iii) first line CRC cytostatic agent 5-fluorouracil (5-FU) on GLO1 protein level in two colorectal cancer cell lines in vitro. |
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