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@article{1604798,
author = {Martišová, Andrea and Sommerová, Lucia and Chalásová, Katarína and Podhorec, Ján and Vojtěšek, Bořivoj and Kaňková, Kateřina and Hrstka, Roman},
article_location = {ATHENS},
article_number = {5},
doi = {http://dx.doi.org/10.3892/ol.2019.10800},
keywords = {AGR2; diabetes mellitus; colorectal cancer; AMPK; autophagy; ROS},
language = {eng},
issn = {1792-1074},
journal = {Oncology letters},
title = {AGR2 silencing contributes to metformin-dependent sensitization of colorectal cancer cells to chemotherapy},
url = {http://dx.doi.org/10.3892/ol.2019.10800},
volume = {18},
year = {2019}
}
TY - JOUR
ID - 1604798
AU - Martišová, Andrea - Sommerová, Lucia - Chalásová, Katarína - Podhorec, Ján - Vojtěšek, Bořivoj - Kaňková, Kateřina - Hrstka, Roman
PY - 2019
TI - AGR2 silencing contributes to metformin-dependent sensitization of colorectal cancer cells to chemotherapy
JF - Oncology letters
VL - 18
IS - 5
SP - 4964-4973
EP - 4964-4973
PB - SPANDIDOS PUBL LTD
SN - 17921074
KW - AGR2
KW - diabetes mellitus
KW - colorectal cancer
KW - AMPK
KW - autophagy
KW - ROS
UR - http://dx.doi.org/10.3892/ol.2019.10800
L2 - http://dx.doi.org/10.3892/ol.2019.10800
N2 - 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.
ER -
MARTIŠOVÁ, Andrea, Lucia SOMMEROVÁ, Katarína CHALÁSOVÁ, Ján PODHOREC, Bořivoj VOJTĚŠEK, Kateřina KAŇKOVÁ and Roman HRSTKA. AGR2 silencing contributes to metformin-dependent sensitization of colorectal cancer cells to chemotherapy. \textit{Oncology letters}. ATHENS: SPANDIDOS PUBL LTD, 2019, vol.~18, No~5, p.~4964-4973. ISSN~1792-1074. Available from: https://dx.doi.org/10.3892/ol.2019.10800.
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