| 周晓刚,王 凯,沈小刚,王 林,覃先鹏,郭志义.RNAi沉默Snail增加结肠癌对5氟尿嘧啶敏感性研究[J].,2017,17(10):1818-1821 |
| RNAi沉默Snail增加结肠癌对5氟尿嘧啶敏感性研究 |
| Suppression of Snail by Short Interfering RNA Enhanced 5-fluorouracil-induced Cell Death in Colon Cancer Cells |
| 投稿时间：2016-07-12 修订日期：2016-08-10 |
| DOI：10.13241/j.cnki.pmb.2017.10.005 |
| 中文关键词: 上皮间质转化 结肠癌 5氟尿嘧啶 Snail |
| 英文关键词: Epithelial-to-mesenchymal transition Colon cancer 5-fluorouracil Snail |
| 基金项目:国家自然科学基金青年科学基金项目（81301910） |
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| 中文摘要: |
| 摘要 目的：研究Snail的抑制是否能增加耐药结肠癌细胞对5-FU的敏感性，评估其可能的信号转导通路。方法：使用5-氟尿嘧啶耐药 HCT116细胞（HCT116／5-FU），评估细胞形态及分子的变化。通过靶向人Snail基因小干扰RNA（siRNA）抑制Snail的表达。Annexin V/PI染色用于评估5-FU诱导的细胞凋亡。Western blot检测caspase以及可能的丝裂原活化蛋白激酶（MAPK）和线粒体途径。结果：HCT116细胞对5-Fu耐药性的获得诱导了与EMT一致的形态学变化。RNA干扰沉默Snail逆转HCT116／5-FU细胞EMT并增加了5-FU耐药HCT116细胞对5-FU的敏感性。可能的机制涉及JNK与线粒体途径的激活。结论：EMT样表型的改变与HCT116细胞对5-FU耐药相关；siRNA介导的Snail下调可能是一个潜在的克服5-FU化疗耐药的治疗方法。 |
| 英文摘要: |
| ABSTRACT Objective: We tested whether Snail suppression could increase the sensitivity of 5-FU-resistant colon cancer cells to 5-FU and further assessed possible signaling transduction pathways. Methods: Using a 5-fluorouracil-resistant HCT116 cells (HCT116/5-FU), we assessed the cellular morphology and molecular changes consistent with EMT. Expression of Snail was suppressed using a small interfering RNA (siRNA) targeting human Snail mRNA. Annexin V/propidium iodide (PI) apoptosis assay was performed to assess the 5-FU -induced apoptosis. The Caspase as well as possible MAPKs and mitochondrial pathways were determined by Western blot. Results: Acquisition of 5-FU resistance induces morphologic changes consistent with EMT in HCT116 cells. Silencing of Snail by RNA interference reversed the EMT of HCT116/5-FU cells and increased the sensitivity of 5-FU-resistant HCT116 cells to 5-FU, the possible mechanism involve activation of JNK/mitochondrial pathway. Conclusion: EMT-like phenotypic changes is associated with 5-FU resistance in HCT116 cells. siRNA-mediated Snail knockdown could be a potential novel therapeutic approach to overcoming chemoresistance during 5-FU chemotherapy. |
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