title: The effect of p53 gene expression on the inhibition of cell proliferation by paclitaxel.
abstract: OBJECTIVE
  We evaluated the relationship between p53 status and paclitaxel (PTX)-induced inhibition of the growth of human stomach cancer cells.
  
  
  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 muM 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 muM 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-alpha, antagonized the expression of the cleaved form of caspase-3 in MKN45 cells.
  
  
  CONCLUSIONS
  Both p53 status and cyclin-B1 expression might be useful for predicting the therapeutic response of stomach cancer to PTX.
authors.affiliation: Department of Surgical Oncology, Gifu Graduate School of Medicine, 1-1 Yanagido, Gifu City, Japan.
authors.forename: Fumio
authors.initials: F
authors.lastname: Sakashita
authors.forename: Shinji
authors.initials: S
authors.lastname: Osada
authors.forename: Masao
authors.initials: M
authors.lastname: Takemura
authors.forename: Hisashi
authors.initials: H
authors.lastname: Imai
authors.forename: Hiroyuki
authors.initials: H
authors.lastname: Tomita
authors.forename: Kenichi
authors.initials: K
authors.lastname: Nonaka
authors.forename: Takao
authors.initials: T
authors.lastname: Takahashi
authors.forename: Mitsuru
authors.initials: M
authors.lastname: Seishima
mesh_terms: D000972:Antineoplastic Agents, Phytogenic / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects*; D015153:Blotting, Western; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects*; D003001:Cloning, Molecular; D019926:Cyclin B / Q000235:genetics; D056744:Cyclin B1; D004305:Dose-Response Relationship, Drug; D015870:Gene Expression; D006801:Humans; D017239:Paclitaxel / Q000494:pharmacology*; D011237:Predictive Value of Tests; D016159:Tumor Suppressor Protein p53 / Q000235:genetics*
chemical_list: D000972:Antineoplastic Agents, Phytogenic; C534699:CCNB1 protein, human; D019926:Cyclin B; D056744:Cyclin B1; D016159:Tumor Suppressor Protein p53; D017239:Paclitaxel