Pathophysiological link between diabetes and colorectal cancer: effect of diabetic microenvironment, metformin and 5-fluorouracil on AMPK activation, apoptosis and autophagy
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| Year of publication | 2017 |
| Type | Conference abstract |
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| Description | Epidemiologic studies showed that (i) type 2 diabetes mellitus is associated with increased risk of development of certain cancers including colorectal cancer (CRC)and (ii) result of CRC treatment are worse in diabetics including higher mortality rates. On the other hand, antidiabetic treatment, specifically metformin, was associated with better prognosis and also increased efficacy of standard chemotherapeutic treatment of CRC. Despite the historical use, molecular mechanisms of anticancer effect of metformin are not fully understood yet. Activation of AMP-activated protein kinase (AMPK), the key regulator of glucose metabolism, orchestrates the pleiotropic effects of AMPK including cell cycle arrest, autophagy induction or apoptosis but also activation of survival metabolic pathways. It is therefore obvious that the final outcome of metformin action in cancer critically depends on the functionality of p53 as a key regulator of all above mentioned processes. Little is known about how hyperglycaemia/diabetic milieu affects AMPK pathway. Aim of the study was to study the effect of (i) diabetic microenvironment, (ii) metformin and (iii) first line CRC cytostatic agent 5-fluorouracil on AMPK signalling, autophagy and apoptosis in vitro in CRC with defined p53 status. |
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