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Differential sensitivity of paclitaxel-induced apoptosis in human esophageal squamous cell carcinoma cell lines

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Abstract

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.

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Acknowledgements

We Thank to Dr. T. Nishihira (Tohoku University School of Medicine, Japan) for providing the TE cell lines. Dr. H. Coley (University of Surrey, UK) for valuable discussion. This work has supported by Grants-in-Aid from the Ministry of Education, Culture, Sports, Science and Technology, Japan for A.F. and Grants-in-Aid for Scientific Research (C) 15591730 from the Ministry of Education, Science, Sports and Culture of Japan for L.S.F.

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Authors and Affiliations

  1. Department of General Surgical Science (Surgery I), Graduate School of Medicine, Gunma University, 3-39-22, Showa-machi, Maebashi, Gunma, 371-8511, Japan

    Ahmad Faried, Hitoshi Kimura, Makoto Sohda, Masanobu Nakajima, Tatsuya Miyazaki, Hiroyuki Kato & Hiroyuki Kuwano

  2. Department of Gynecology and Reproductive Medicine, Graduate School of Medicine, Gunma University, Maebashi, Gunma, 371-8511, Japan

    Leri S. Faried & Tatsuya Kanuma

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  1. Ahmad Faried
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Correspondence to Ahmad Faried.

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A. Faried and L.S. Faried contributed equally to this project and are considered co-first authors.

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Faried, A., Faried, L.S., Kimura, H. et al. Differential sensitivity of paclitaxel-induced apoptosis in human esophageal squamous cell carcinoma cell lines. Cancer Chemother Pharmacol 57, 301–308 (2006). https://doi.org/10.1007/s00280-005-0038-z

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  • DOI: https://doi.org/10.1007/s00280-005-0038-z

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