Informace o publikaci

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

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MARTISOVA Andrea SOMMEROVA Lucia CHALÁSOVÁ Katarína PODHOREC Jan VOJTESEK Borivoj KAŇKOVÁ Kateřina HRSTKA Roman

Rok publikování 2019
Druh Článek v odborném periodiku
Časopis / Zdroj Oncology letters
Fakulta / Pracoviště MU

Lékařská fakulta

Citace
www http://dx.doi.org/10.3892/ol.2019.10800
Doi http://dx.doi.org/10.3892/ol.2019.10800
Klíčová slova AGR2; diabetes mellitus; colorectal cancer; AMPK; autophagy; ROS
Popis 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.
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