由于ER应激反应的应激反应,耐DCF的ESCC在与通道阻断剂相结合时重新发展药物敏感性
Wenjie Liao1, Satoru Matsuda2, Tetsuya Takimoto3
1Department of Surgery, Keio University School of Medicine, 35 Shinanomachi, Shinjuku-Ku, Tokyo, 160-8582, Japan.
可以克服食道状细胞癌 (ESCC) 中的化疗耐药性. 结合多塞塔克塞尔,西斯和5-甲 (DCF) 治疗与通道阻断剂 (CCBs) 的结合,通过增强内分泌网膜应激,使耐性ESCC细胞重新敏感.
科学领域:
- 在瘤学瘤学.
- 药理学 药理学是指药理学的学科.
- 分子生物学分子生物学
背景情况:
- 食道状细胞癌 (ESCC) 经常表现出对标准的多塞塔克塞尔/西斯普拉丁/5-甲 (DCF) 化疗的耐药性.
- 克服这种化学抵抗是ESCC治疗中关键的未满足的临床需求.
研究的目的:
- 研究ESCC中DCF电阻的机制.
- 评估通道阻断剂 (CCB) 在克服ESCC中DCF抵抗方面的有效性.
主要方法:
- 通过长时间暴露于药物,建立了耐DCF的ESCC细胞系.
- 用于转录组分析的RNA测序,以确定参与抗性的分子途径.
- 功能性测试,以评估CCBs对细胞活性的影响,与DCF疗法结合使用.
主要成果:
- 转录基因分析发现DCF抗性ESCC细胞中的内质网膜 (ER) 应激通路的丰富.
- 与DCF和各种CCB的联合治疗表明,在耐药细胞系中恢复了化学敏感性.
- CCBs增强了ER应激反应,有助于重新敏感化.
结论:
- 联合DCF和CCB疗法通过增加ER压力,使DCF抵抗ESCC细胞重新敏感.
- 在ESCC化疗中重新使用CCB作为辅助剂是一个有前途的治疗策略.
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