Differential sensitivity of paclitaxel-induced apoptosis in human esophageal squamous cell carcinoma cell lines
Differential sensitivity of paclitaxel-induced apoptosis in human esophageal squamous cell carcinoma cell lines
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DOI：
10.1007/s00280-005-0038-z
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发表时间：
2006-03-01
影响因子：
3
通讯作者：
Kuwano, H
中科院分区：
文献类型：
--
作者：
Faried, A;Faried, LS;Kuwano, H
目的：紫杉醇是一种高效的食管腺癌和鳞状细胞癌化疗药物。然而，其在人食管癌细胞中的确切作用尚不清楚。本研究旨在研究紫杉醇激活的检查点的细胞周期阶段之间的关系，并阐明紫杉醇在人食管鳞状细胞癌（ESCC）细胞系中的作用的分子途径。方法：检测TE-2、TE-13和TE-14三种人食管鳞癌细胞系对紫杉醇的反应。使用MTT测定，用不同浓度的紫杉醇处理ESCC细胞1-3天。流式细胞仪检测细胞周期进程和凋亡。进行DNA片段化测定以确认片段化的细胞作为凋亡细胞的标志。此外，通过Western印迹分析检测经ESC处理的细胞中凋亡相关蛋白的表达。结果：TE-14细胞对肿瘤的敏感性最高。紫杉醇诱导食管鳞癌细胞凋亡前出现G2/M期阻滞。流式细胞术和DNA梯状条带形成观察到药物处理的TE-13和TE-14细胞染色质断裂。相比之下，TE-2细胞的测量结果更提示表型a对紫杉醇治疗有抗性。Western blot分析结果表明，线粒体途径可能参与紫杉醇诱导食管鳞癌细胞凋亡。结论：观察到不同的敏感性，在人食管鳞癌细胞株，对紫杉醇治疗的反应。G2/M期阻滞发生在紫杉醇诱导的细胞凋亡之前，可能是由线粒体（内在）凋亡途径介导的。
Purpose: Paclitaxel is a highly effective chemotherapy agent against adenocarcinomas and squamous cell carcinomas of the esophagus. However, its precise effects in human esophageal cancer cells are not well understood. This study was designed to examine the relationship between cell-cycle phases of paclitaxel-activated checkpoints and to elucidate the molecular pathway of the effect of paclitaxel in human esophageal squamous cell carcinoma (ESCC) cell lines. Methods: The three human ESCC cell lines-TE-2, TE-13 and TE-14-were examined for their response to paclitaxel. ESCC cells were treated with various concentrations of paclitaxel for 1-3 days using MTT assay. The cell-cycle progression and apoptosis were examined by flow cytometry. DNA fragmentation assay was carried out to confirm the fragmented cells as hallmark for apoptotic cells. In additional, the expression of apoptosis-related proteins in ESCC-treated cells was then examined by Western blot analysis. Results: TE-14 cells demonstrated the highest sensitivity among all cells. G2/M cell-cycle arrest occurs prior to paclitaxel-induced apoptosis in ESCC cells. The fragmentation of chromatin was observed in drug treated TE-13 and TE-14 cells by flow cytometry and DNA ladder formation. In contrast, the measurement for TE-2 cells was more suggestive of phenotype a resistant in response to paclitaxel treatment. Western blot analysis results showed that the mitochondrial pathway might be involved in paclitaxel-induced apoptosis in ESCC cell lines. Conclusion: Differential sensitivity was observed in human ESCC cell lines in response to paclitaxel treatment. G2/M arrest occurs with a prior to paclitaxel-induced apoptosis and might be mediated by the mitochondrial (intrinsic) apoptosis pathway in human ESCC cells.