Mir-148a improves response to chemotherapy in sensitive and resistant oesophageal adenocarcinoma and squamous cell carcinoma cells

Richard Hummel, David Watson, Cameron Smith, Jakob Kist, Michael Michael, Joerg Haier, Damian Hussey

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    84 Citations (Scopus)

    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.

    Original languageEnglish
    Pages (from-to)429-438
    Number of pages10
    JournalJournal of Gastrointestinal Surgery
    Volume15
    Issue number3
    DOIs
    Publication statusPublished - Mar 2011

    Keywords

    • Chemotherapy
    • miR-106a
    • miR-148a
    • miRNA
    • Resistance

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