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

Mir-148a Improves Response to Chemotherapy in Sensitive and Resistant Oesophageal Adenocarcinoma and Squamous Cell Carcinoma Cells
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DOI:
10.1007/s11605-011-1418-9
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发表时间:
2011-03-01
影响因子:
3.2
通讯作者:
Hussey, Damian J.
Hussey, Damian J.
中科院分区:
医学3区
文献类型:
--
作者:
Hummel, Richard;Watson, David I.;Hussey, Damian J.

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背景晚期食管癌患者对化疗的反应差异很大。我们研究了操纵某些microRNA对食管癌细胞对顺铂和5-氟尿嘧啶(5-FU)反应的影响。方法建立顺铂/5-氟尿嘧啶耐药的食管鳞状细胞癌(SCC)和腺癌(EAC)细胞系,结果miR-106 a和miR-148 a异位上调对两种药物治疗效果的影响不一致。上调后,化疗敏感性EAC细胞对顺铂的敏感性降低(细胞存活率,+8.7 +/-0.8%; p = 0.003),顺铂耐药EAC细胞对5-FU的反应改善(细胞存活率,-6.4 +/-2.5%; p = 0.011)。miR-148 a上调显著增加了10种细胞系中7种对化疗的敏感性,表现为顺铂后细胞活力降低22.6 +/- 7.9%至50.5 +/- 10.6%(p
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