Open AccessFOXO1 inactivation induces cisplatin resistance in bladder cancer
Author(s) -
Ide Hiroki,
Goto Takuro,
Teramoto Yuki,
Mizushima Taichi,
Jiang Guiyang,
Nagata Yujiro,
Inoue Satoshi,
Baras Alexander S.,
Kashiwagi Eiji,
Miyamoto Hiroshi
Publication year - 2020
Publication title -
cancer science
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.035
H-Index - 141
eISSN - 1349-7006
pISSN - 1347-9032
DOI - 10.1111/cas.14557
Subject(s) - cisplatin , foxo1 , western blot , immunohistochemistry , chemotherapy , bladder cancer , cancer , medicine , cancer research , oncology , biology , phosphorylation , gene , biochemistry , protein kinase b
We found that FOXO1‐shRNA sublines or FOXO1‐positive cells co–treated with a FOXO1 inhibitor were significantly more resistant to cisplatin treatment at pharmacological concentrations, compared with respective control sublines or those with mock treatment. Western blot demonstrated considerable increases in the expression levels of a phosphorylated inactive form of FOXO1 (p‐FOXO1) in cisplatin‐resistant sublines established by long‐term culture with low/increasing doses of cisplatin, compared with respective controls. Immunohistochemistry in surgical specimens from patients with muscle‐invasive bladder cancer undergoing cisplatin‐based neoadjuvant therapy further showed a strong trend to associate between p‐FOXO1 positivity and unfavorable response to chemotherapy.