FOXO1 inactivation induces cisplatin resistance in bladder cancer.

Abstract

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.

• Authors: Hiroki Ide, Takuro Goto, Yuki Teramoto, Taichi Mizushima, Guiyang Jiang, Yujiro Nagata, Satoshi Inoue, Alexander S Baras, Eiji Kashiwagi, Hiroshi Miyamoto
• Journal: Cancer science (Cancer Sci) Vol. 111 Issue 9 Pg. 3397-3400 (Sep 2020) ISSN: 1349-7006 [Electronic] England
• PMID: 32678492 (Publication Type: Letter)
• Copyright: © 2020 The Authors. Cancer Science published by John Wiley & Sons Australia, Ltd on behalf of Japanese Cancer Association.

Chemical References

• Antineoplastic Agents
• FOXO1 protein, human
• Forkhead Box Protein O1
• Cisplatin

Topics

• Antineoplastic Agents (pharmacology)
• Cisplatin (pharmacology)
• Drug Resistance, Neoplasm (genetics)
• Forkhead Box Protein O1 (genetics, metabolism)
• Gene Expression
• Gene Silencing
• Humans
• Immunohistochemistry
• Urinary Bladder Neoplasms (drug therapy, genetics, metabolism)