Pathophysiological link between diabetes and colorectal cancer:
effect of diabetic microenvironment, metformin and
5-fluorouracil on AMPK activation, apoptosis and autophagy

a 2017

Pathophysiological link between diabetes and colorectal cancer: effect of diabetic microenvironment, metformin and 5-fluorouracil on AMPK activation, apoptosis and autophagy

CHALÁSOVÁ, Katarína, Lukáš PÁCAL, Petr MÜLLER, Roman HRSTKA, Kateřina KAŇKOVÁ et. al.

Základní údaje

Originální název

Pathophysiological link between diabetes and colorectal cancer: effect of diabetic microenvironment, metformin and 5-fluorouracil on AMPK activation, apoptosis and autophagy

Autoři

CHALÁSOVÁ, Katarína, Lukáš PÁCAL, Petr MÜLLER, Roman HRSTKA a Kateřina KAŇKOVÁ

Vydání

53rd EASD Annual Meeting, 2017

Další údaje

Typ výsledku

Konferenční abstrakt

Utajení

není předmětem státního či obchodního tajemství

Klíčová slova česky

diabetes mellitus; kolorektální karcinom; metformin

Klíčová slova anglicky

diabetes mellitus; colorectal cancer; metformin

Změněno: 27. 9. 2017 22:52, Mgr. Lukáš Pácal, Ph.D.

Anotace

V originále

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.

Návaznosti

GA16-14829S, projekt VaV

Název: Efekt diabetického mikroprostředí na vybrané procesy při vzniku kolorektálního karcinomu, jeho klinický průběh a odpověď na terapii

Investor: Grantová agentura ČR, Efekt diabetického mikroprostředí na vybrané procesy při vzniku kolorektálního karcinomu, jeho klinický průběh a odpověď na terapii

Citovat

CHALÁSOVÁ, Katarína, Lukáš PÁCAL, Petr MÜLLER, Roman HRSTKA a Kateřina KAŇKOVÁ. Pathophysiological link between diabetes and colorectal cancer: effect of diabetic microenvironment, metformin and 5-fluorouracil on AMPK activation, apoptosis and autophagy. In 53rd EASD Annual Meeting. 2017.

@proceedings{1389937,
   author = {Chalásová, Katarína and Pácal, Lukáš and Müller, Petr and Hrstka, Roman and Kaňková, Kateřina},
   booktitle = {53rd EASD Annual Meeting},
   keywords = {diabetes mellitus; colorectal cancer; metformin},
   title = {Pathophysiological link between diabetes and colorectal cancer: effect of diabetic microenvironment, metformin and 5-fluorouracil on AMPK activation, apoptosis and autophagy},
   year = {2017}
}

TY  - CONF
ID  - 1389937
AU  - Chalásová, Katarína - Pácal, Lukáš - Müller, Petr - Hrstka, Roman - Kaňková, Kateřina
PY  - 2017
TI  - Pathophysiological link between diabetes and colorectal cancer: effect of diabetic microenvironment, metformin and 5-fluorouracil on AMPK activation, apoptosis and autophagy
KW  - diabetes mellitus
KW  - colorectal cancer
KW  - metformin
N2  - 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.
ER  -

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