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Journal of Gastrointestinal Surgery

Published in:

01-03-2011 | Original Article

Mir-148a Improves Response to Chemotherapy in Sensitive and Resistant Oesophageal Adenocarcinoma and Squamous Cell Carcinoma Cells

Authors: Richard Hummel, David I. Watson, Cameron Smith, Jakob Kist, Michael Z. Michael, Joerg Haier, Damian J. Hussey

Published in: Journal of Gastrointestinal Surgery | Issue 3/2011

Abstract

Background

Response to chemotherapy varies widely in patients with advanced oesophageal cancer. We investigated the impact of manipulating certain microRNAs on response to cisplatin and 5-fluorouracil (5-FU) in oesophageal cancer cells.

Methods

Cisplatin-/5-fluorouracil-resistant oesophageal squamous cell carcinoma (SCC) and adenocarcinoma (EAC) cell lines were established, and the impact of ectopic upregulation of miR-106a and miR-148a on response to both drugs was assessed.

Results

The impact of miR-106a-upregulation was inconsistent. Upregulation was followed by reduced sensitivity to cisplatin in chemotherapy-sensitive EAC cells (cell survival, +8.7 ± 0.8%; p = 0.003) and an improved response to 5-FU in cisplatin-resistant EAC cells (cell survival, −6.4 ± 2.5%; p = 0.011). MiR-148a upregulation significantly increased sensitivity to chemotherapy in seven out of ten cell lines, represented by a decrease in cell viability of 22.6 ± 7.9% to 50.5 ± 10.6% after cisplatin (p ≤ 0.014) and 6.0 ± 0.8% to 15.0 ± 4.1% after 5-FU treatment (p ≤ 0.012). The only cell lines in which miR-148a upregulation had no effect were cisplatin-resistant EAC exposed to cisplatin and 5-FU-sensitive and 5-FU-resistant SCC cells exposed to 5-FU.

Conclusion

MiR-148a sensitized chemotherapy-sensitive oesophageal cancer cell lines to cisplatin and, to a lesser extent, to 5-flurouracil and attenuated resistance in chemotherapy-resistant variants. Further experimental and clinical studies to investigate the exact mechanisms involved are warranted.

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Title: Mir-148a Improves Response to Chemotherapy in Sensitive and Resistant Oesophageal Adenocarcinoma and Squamous Cell Carcinoma Cells
Authors: Richard Hummel
David I. Watson
Cameron Smith
Jakob Kist
Michael Z. Michael
Joerg Haier
Damian J. Hussey
Publication date: 01-03-2011
Publisher: Springer-Verlag
Published in: Journal of Gastrointestinal Surgery / Issue 3/2011
Print ISSN: 1091-255X
Electronic ISSN: 1873-4626
DOI: https://doi.org/10.1007/s11605-011-1418-9

At a glance: The ONWARDS insulin icodec trials

Springer Medicine

Mir-148a Improves Response to Chemotherapy in Sensitive and Resistant Oesophageal Adenocarcinoma and Squamous Cell Carcinoma Cells

Abstract

Background

Methods

Results

Conclusion

At a glance: The ONWARDS insulin icodec trials

Springer Medicine

Abstract

Background

Methods

Results

Conclusion

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