The involvement of FOXO1 in cytotoxic stress and drug-resistance induced by paclitaxel in ovarian cancers

被引：61

作者：

Goto, T. ^{[1
]}

Takano, M. ^{[2
]}

Hirata, J. ^{[2
]}

Tsuda, H. ^{[3
]}

机构：

[1] Saitama Med Univ, Int Med Ctr Comprehens Canc Ctr, Dept Gynaecol Oncol, Hidaka City, Saitama 3501298, Japan

[2] Natl Def Med Coll, Dept Obstet & Gynaecol, Tokorozawa, Saitama 3598513, Japan

[3] Natl Def Med Coll, Dept Pathol 2, Tokorozawa, Saitama 3598513, Japan

来源：

BRITISH JOURNAL OF CANCER | 2008年 / 98卷 / 06期

关键词：

ovarian cancer; paclitaxel; FOXO1; drug resistance; reactive oxygen spices (ROS);

D O I：

10.1038/sj.bjc.6604279

中图分类号：

R73 [肿瘤学];

学科分类号：

100214 ;

摘要：

The role of transcriptional factor FOXO1 in the mechanism of drug- resistance in ovarian cancer has not been elucidated. In ovarian cancer cell lines, FOXO1 expression and its correlation with paclitaxel treatment was investigated by cytotoxic assay and silencing experiment. Clinical ovarian cancer samples were also examined for FOXO1 expression by immunohistochemistry. FOXO1 expression was distinctively upregulated in paclitaxel- resistant cell line, and enhanced by exposure to paclitaxel. FOXO1 overexpression was frequently observed in tissue samples from chemoresistant patients compared to chemosensitive patients. FOXO1 silencing in paclitaxel- resistant cell line decreased its resistance. Modification of oxidative stress by co- treatment with pharmacologic modulators of reactive oxygen species attenuated cytotoxicity of paclitaxel. Downstream targets of FOXO1 involving oxidative stress were also attenuated in silencing experiment, suggesting its involvement in altered sensitivity to paclitaxel. These results indicate that FOXO1 links to cytotoxic stress induced by paclitaxel and contributes to the drug- resistance in ovarian cancers.

引用

页码：1068 / 1075

页数：8

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