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Nrf2/keap1‐pathway activation and reduced susceptibility to chemotherapy treatment by acidification in esophageal adenocarcinoma cells

Publication ,  Journal Article
Storz, L; Walther, P; Chemnitzer, O; Lyros, O; Niebisch, S; Mehdorn, M; Jansen‐winkeln, B; Moulla, Y; Büch, T; Gockel, I; Thieme, R
Published in: Cancers
June 1, 2021

Chronic acid reflux causes cellular damage and inflammation in the lower esophagus. Due to these irritating insults, the squamous epithelium is replaced by metaplastic epithelium, which is a risk factor for the development of esophageal adenocarcinoma (EAC). In this study, we investigated the acid susceptibility in a Barrett’s cell culture in vitro model, using six cell lines, derived from squamous epithelium (EPC1 and EPC2), metaplasia (CP‐A), dysplasia (CP‐B), and EAC (OE33 and OE19) cells. Cells exposed to acidic pH showed a decreased viability dependent on time, pH, and progression status in the Barrett’s sequence, with the highest acid susceptibility in the squamous epithelium (EPC1 and EPC2), and the lowest in EAC cells. Acid pulsing was accompanied with an activation of the Nrf2/Keap1‐ and the NFκB‐pathway, resulting in an increased expression of HO1—independent of the cellular context. OE33 showed a decreased responsiveness towards 5‐FU, when the cells were grown in acidic conditions (pH 6 and pH 5.5). Our findings suggest a strong damage of squamous epithelium by gastroesophageal reflux, while Barrett’s dysplasia and EAC cells apparently exert acid‐protective features, which lead to a cellular resistance against acid reflux.

Duke Scholars

Published In

Cancers

DOI

EISSN

2072-6694

Publication Date

June 1, 2021

Volume

13

Issue

11

Related Subject Headings

  • 3211 Oncology and carcinogenesis
  • 1112 Oncology and Carcinogenesis
 

Citation

APA
Chicago
ICMJE
MLA
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Storz, L., Walther, P., Chemnitzer, O., Lyros, O., Niebisch, S., Mehdorn, M., … Thieme, R. (2021). Nrf2/keap1‐pathway activation and reduced susceptibility to chemotherapy treatment by acidification in esophageal adenocarcinoma cells. Cancers, 13(11). https://doi.org/10.3390/cancers13112806
Storz, L., P. Walther, O. Chemnitzer, O. Lyros, S. Niebisch, M. Mehdorn, B. Jansen‐winkeln, et al. “Nrf2/keap1‐pathway activation and reduced susceptibility to chemotherapy treatment by acidification in esophageal adenocarcinoma cells.” Cancers 13, no. 11 (June 1, 2021). https://doi.org/10.3390/cancers13112806.
Storz L, Walther P, Chemnitzer O, Lyros O, Niebisch S, Mehdorn M, et al. Nrf2/keap1‐pathway activation and reduced susceptibility to chemotherapy treatment by acidification in esophageal adenocarcinoma cells. Cancers. 2021 Jun 1;13(11).
Storz, L., et al. “Nrf2/keap1‐pathway activation and reduced susceptibility to chemotherapy treatment by acidification in esophageal adenocarcinoma cells.” Cancers, vol. 13, no. 11, June 2021. Scopus, doi:10.3390/cancers13112806.
Storz L, Walther P, Chemnitzer O, Lyros O, Niebisch S, Mehdorn M, Jansen‐winkeln B, Moulla Y, Büch T, Gockel I, Thieme R. Nrf2/keap1‐pathway activation and reduced susceptibility to chemotherapy treatment by acidification in esophageal adenocarcinoma cells. Cancers. 2021 Jun 1;13(11).

Published In

Cancers

DOI

EISSN

2072-6694

Publication Date

June 1, 2021

Volume

13

Issue

11

Related Subject Headings

  • 3211 Oncology and carcinogenesis
  • 1112 Oncology and Carcinogenesis