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The effect of p53 gene expression on the inhibition of cell proliferation by paclitaxel

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Abstract

Background/Aims

We evaluated the relationship between p53 status and paclitaxel (PTX)-induced inhibition of the growth of human stomach cancer cells.

Materials and methods

We made use of two human stomach cancer cell lines, MKN45 and MKN28. Growth inhibition in response to PTX was evaluated by MTT method. We used flow cytometry to monitor the cell cycle and western blot analysis to evaluate the expression of signaling molecules.

Results

PTX inhibited the proliferation of both stomach cancer cell lines in a dose-dependent manner. However, PTX cytotoxicity was stronger in MKN28 cells. Flow cytometric analysis showed that 1 μM PTX enhanced the percentage of MKN 45 cells in the sub-G1 phase of the cell cycle, whereas it increased the percentage of MKN 28 cells arrested at G2/M phase. 1 μM PTX was found to increase cyclin B1 production in MKN28 cells, but not in MKN 45 cells. In contrast, PTX-treatment led to an increase in the cleaved form of caspase-3 in MKN45, but not MKN28 cells. An inhibitor of p53, pifithrin-α, antagonized the expression of the cleaved form of caspase-3 in MKN45 cells.

Conclusion

Both p53 status and cyclin-B1 expression might be useful for predicting the therapeutic response of stomach cancer to PTX.

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Authors and Affiliations

  1. Department of Surgical Oncology, Gifu Graduate School of Medicine, 1-1 Yanagido, Gifu City, 501-1194, Japan

    Fumio Sakashita, Shinji Osada, Hisashi Imai, Hiroyuki Tomita, Kenichi Nonaka & Takao Takahashi

  2. Department of Informative Clinical Medicine, Gifu Graduate School of Medicine, 1-1 Yanagido, Gifu City, 501-1194, Japan

    Masao Takemura & Mitsuru Seishima

Authors
  1. Fumio Sakashita
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  2. Shinji Osada
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  3. Masao Takemura
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  4. Hisashi Imai
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  5. Hiroyuki Tomita
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Correspondence to Shinji Osada.

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Sakashita, F., Osada, S., Takemura, M. et al. The effect of p53 gene expression on the inhibition of cell proliferation by paclitaxel. Cancer Chemother Pharmacol 62, 379–385 (2008). https://doi.org/10.1007/s00280-007-0614-5

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  • DOI: https://doi.org/10.1007/s00280-007-0614-5

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