title: Differential sensitivity of paclitaxel-induced apoptosis in human esophageal squamous cell carcinoma cell lines.
abstract: OBJECTIVE
  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.
  
  
  CONCLUSIONS
  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.
authors: Department of General Surgical Science (Surgery I), Graduate School of Medicine, Gunma University, Showa-machi, Maebashi, Japan. afaried@med.gunma-u.ac.jp
authors: Ahmad
authors: A
authors: Faried
authors: Leri S
authors: LS
authors: Faried
authors: Hitoshi
authors: H
authors: Kimura
authors: Makoto
authors: M
authors: Sohda
authors: Masanobu
authors: M
authors: Nakajima
authors: Tatsuya
authors: T
authors: Miyazaki
authors: Hiroyuki
authors: H
authors: Kato
authors: Tatsuya
authors: T
authors: Kanuma
authors: Hiroyuki
authors: H
authors: Kuwano
mesh_terms: D000972:Antineoplastic Agents, Phytogenic / Q000494:pharmacology; D017209:Apoptosis / Q000187:drug effects* / Q000502:physiology; D051017:Apoptosis Regulatory Proteins / Q000378:metabolism; D015153:Blotting, Western / Q000379:methods; D002294:Carcinoma, Squamous Cell / Q000378:metabolism / Q000473:pathology; D045744:Cell Line, Tumor; D053938:DNA Fragmentation / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D004938:Esophageal Neoplasms / Q000378:metabolism / Q000473:pathology; D005434:Flow Cytometry / Q000379:methods; D016195:G2 Phase / Q000187:drug effects / Q000502:physiology; D006801:Humans; D017239:Paclitaxel / Q000494:pharmacology*; D013997:Time Factors; D050257:Tubulin Modulators / Q000494:pharmacology
chemical_list: D000972:Antineoplastic Agents, Phytogenic; D051017:Apoptosis Regulatory Proteins; D050257:Tubulin Modulators; D017239:Paclitaxel