Mir-148a improves response to chemotherapy in sensitive and resistant oesophageal adenocarcinoma and squamous cell carcinoma cells
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Mir-148a improves response to chemotherapy in sensitive and resistant oesophageal adenocarcinoma and squamous cell carcinoma cells. / Hummel, Richard; Watson, David I; Smith, Cameron; Kist, Jakob; Michael, Michael Z; Haier, Joerg; Hussey, Damian J.
In: Journal of gastrointestinal surgery : official journal of the Society for Surgery of the Alimentary Tract, Vol. 15, No. 3, 03.2011, p. 429-38.Research output: SCORING: Contribution to journal › SCORING: Journal article › Research › peer-review
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TY - JOUR
T1 - Mir-148a improves response to chemotherapy in sensitive and resistant oesophageal adenocarcinoma and squamous cell carcinoma cells
AU - Hummel, Richard
AU - Watson, David I
AU - Smith, Cameron
AU - Kist, Jakob
AU - Michael, Michael Z
AU - Haier, Joerg
AU - Hussey, Damian J
PY - 2011/3
Y1 - 2011/3
N2 - 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.
AB - 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.
KW - Adenocarcinoma
KW - Antimetabolites, Antineoplastic
KW - Carcinoma, Squamous Cell
KW - Cell Line, Tumor
KW - Cell Survival
KW - Cisplatin
KW - Drug Resistance, Neoplasm
KW - Esophageal Neoplasms
KW - Fluorouracil
KW - Humans
KW - MicroRNAs
KW - Transfection
KW - Up-Regulation
U2 - 10.1007/s11605-011-1418-9
DO - 10.1007/s11605-011-1418-9
M3 - SCORING: Journal article
C2 - 21246413
VL - 15
SP - 429
EP - 438
JO - J GASTROINTEST SURG
JF - J GASTROINTEST SURG
SN - 1091-255X
IS - 3
ER -
