The effect of p53 gene expression on the inhibition of cell proliferation by paclitaxel.
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.
Sakashita
Fumio
F
Department of Surgical Oncology, Gifu Graduate School of Medicine, 1-1 Yanagido, Gifu City, Japan.
Osada
Shinji
S
Takemura
Masao
M
Imai
Hisashi
H
Tomita
Hiroyuki
H
Nonaka
Kenichi
K
Takahashi
Takao
T
Seishima
Mitsuru
M
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*
D000972:Antineoplastic Agents, Phytogenic; C534699:CCNB1 protein, human; D019926:Cyclin B; D056744:Cyclin B1; D016159:Tumor Suppressor Protein p53; D017239:Paclitaxel