The effect of p53 gene expression on the inhibition of cell proliferation by paclitaxel
The effect of p53 gene expression on the inhibition of cell proliferation by paclitaxel
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DOI：
10.1007/s00280-007-0614-5
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发表时间：
2008-08-01
影响因子：
3
通讯作者：
Seishima, Mitsuru
中科院分区：
文献类型：
--
作者：
Sakashita, Fumio;Osada, Shinji;Seishima, Mitsuru
背景/目的我们研究了p53状态与紫杉醇（PTX）诱导的人胃癌细胞生长抑制的关系。材料与方法采用两种人胃癌细胞系MKN45和MKN28。采用MTT法评价PTX对生长的抑制作用。采用流式细胞术监测细胞周期，western blot分析信号分子的表达。结果PTX对两种胃癌细胞系的增殖均呈剂量依赖性。然而，PTX对MKN28细胞的细胞毒性更强。流式细胞术分析显示，1 μ M PTX可提高MKN 45细胞处于细胞周期亚g1期的百分比，而MKN 28细胞处于G2/M期的百分比。1 μ M PTX在MKN28细胞中增加了细胞周期蛋白B1的产生，而在mkn45细胞中没有。相比之下，ptx处理导致MKN45细胞中caspase-3的裂解形式增加，而MKN28细胞中则没有。在MKN45细胞中，p53的一种抑制剂，聚氟乙烯- α，可以拮抗caspase-3的裂解形式的表达。结论p53状态和cyclin-B1表达可能是预测胃癌PTX治疗反应的重要指标。
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 mu M 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 mu M 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.Conclusion Both p53 status and cyclin-B1 expression might be useful for predicting the therapeutic response of stomach cancer to PTX.