J 2019

AGR2 silencing contributes to metformin-dependent sensitization of colorectal cancer cells to chemotherapy

MARTIŠOVÁ, Andrea, Lucia SOMMEROVÁ, Katarína CHALÁSOVÁ, Ján PODHOREC, Bořivoj VOJTĚŠEK et. al.

Basic information

Original name

AGR2 silencing contributes to metformin-dependent sensitization of colorectal cancer cells to chemotherapy

Authors

MARTIŠOVÁ, Andrea (203 Czech Republic), Lucia SOMMEROVÁ (203 Czech Republic), Katarína CHALÁSOVÁ (703 Slovakia, belonging to the institution), Ján PODHOREC (203 Czech Republic), Bořivoj VOJTĚŠEK (203 Czech Republic), Kateřina KAŇKOVÁ (203 Czech Republic, belonging to the institution) and Roman HRSTKA (203 Czech Republic, guarantor)

Edition

Oncology letters, ATHENS, SPANDIDOS PUBL LTD, 2019, 1792-1074

Other information

Language

English

Type of outcome

Článek v odborném periodiku

Field of Study

30204 Oncology

Country of publisher

Greece

Confidentiality degree

není předmětem státního či obchodního tajemství

References:

Impact factor

Impact factor: 2.311

RIV identification code

RIV/00216224:14110/19:00108044

Organization unit

Faculty of Medicine

UT WoS

000503219600064

Keywords in English

AGR2; diabetes mellitus; colorectal cancer; AMPK; autophagy; ROS

Tags

Tags

International impact, Reviewed
Změněno: 31/5/2024 11:10, Mgr. Marie Šípková, DiS.

Abstract

V originále

There is growing epidemiological evidence indicating an association between diabetes mellitus and the increased incidence of colorectal cancer (CRC). The preferred initial and most widely used pharmacological agent for the treatment of type 2 diabetes is metformin, which in parallel reduces the risk of CRC and improves patient prognosis. AMP-activated protein kinase (AMPK) appears to be tightly associated with the beneficial metabolic effects of metformin, serving as a cellular energy sensor activated in response to a variety of conditions that deplete cellular energy levels. Such conditions include nutrient starvation (particularly glucose), hypoxia and exposure to toxins that inhibit the mitochondrial respiratory chain complex. The aim of the present study was to determine the effect of metformin on CRC cell lines, with different levels of anterior gradient 2 (AGR2) expression, exposed to 5-fluorouracil (5-FU) and oxaliplatin, alone or in combination with metformin. AGR2 has recently emerged as a factor involved in colon carcinogenesis. In AGR2-knockout cells, markedly higher levels of phosphorylated-AMPK were observed in comparison with control cells transfected with GFP-scrambled guide RNA, which indicated that the presence of AGR2 may interfere with the metformin-dependent activation of AMPK. In addition, metformin in combination with 5-FU and oxaliplatin induced ROS production and attenuated autophagy. This effect was enhanced in AGR2-knockout cells.

Links

GA16-14829S, research and development project
Name: Efekt diabetického mikroprostředí na vybrané procesy při vzniku kolorektálního karcinomu, jeho klinický průběh a odpověď na terapii
Investor: Czech Science Foundation