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

Abstract

We evaluated the relationship between p53 status and paclitaxel (PTX)-induced inhibition of the growth of human stomach cancer cells. 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. 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. Both p53 status and cyclin-B1 expression might be useful for predicting the therapeutic response of stomach cancer to PTX.