Negative regulation of transcription factor FoxM1 by p53 enhances oxaliplatin-induced senescence in hepatocellular carcinoma

Kai Qu; Xinsen Xu; Chang Liu; Qifei Wu; Jichao Wei; Fandi Meng; Lei Zhou; Zhixin Wang; Lei Lei; Peijun Liu

doi:10.1016/j.canlet.2012.12.008

Negative regulation of transcription factor FoxM1 by p53 enhances oxaliplatin-induced senescence in hepatocellular carcinoma

Cancer Lett. 2013 Apr 30;331(1):105-14. doi: 10.1016/j.canlet.2012.12.008. Epub 2012 Dec 20.

Authors

Kai Qu¹, Xinsen Xu, Chang Liu, Qifei Wu, Jichao Wei, Fandi Meng, Lei Zhou, Zhixin Wang, Lei Lei, Peijun Liu

Affiliation

¹ Department of Hepatobiliary Surgery, First Affiliated Hospital of Medical College, Xi'an Jiaotong University, 277 West Yanta Road, Xi'an 710061, China.

PMID: 23262037
DOI: 10.1016/j.canlet.2012.12.008

Abstract

Previous studies have demonstrated the involvement of transcriptional factor forkhead box M1 (FoxM1) in cellular senescence of hepatocellular carcinoma (HCC). In the present study, we revealed that oxaliplatin could induce senescence in HCC cells, since advanced HCC patients with lower expression of FoxM1 were more sensitive to oxaliplatin therapy. Our data indicated that due to the repression by p53, FoxM1 played a critical role in oxaliplatin-induced senescence via regulating cycle-related proteins p21, p27, cyclins B1 and D1. Furthermore, inhibition of FoxM1, combined with oxaliplatin treatment, could significantly promote the senescence of HCC cells. Taken together, our findings suggest that FoxM1 may represent a promising therapeutic target for the medication of the chemosensitivity to oxaliplatin in HCC patients.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Apoptosis / drug effects
Blotting, Western
Carcinoma, Hepatocellular / drug therapy
Carcinoma, Hepatocellular / metabolism
Carcinoma, Hepatocellular / pathology*
Cell Proliferation / drug effects
Cellular Senescence / drug effects*
Colony-Forming Units Assay
Cyclin-Dependent Kinase Inhibitor p21 / genetics
Cyclin-Dependent Kinase Inhibitor p21 / metabolism
Fluorescent Antibody Technique
Forkhead Box Protein M1
Forkhead Transcription Factors / antagonists & inhibitors
Forkhead Transcription Factors / genetics
Forkhead Transcription Factors / metabolism*
Gene Expression Regulation, Neoplastic / drug effects*
Humans
Immunoenzyme Techniques
Liver Neoplasms / drug therapy
Liver Neoplasms / metabolism
Liver Neoplasms / pathology*
Organoplatinum Compounds / pharmacology*
Oxaliplatin
RNA, Messenger / genetics
RNA, Small Interfering / genetics
Reactive Oxygen Species / metabolism
Real-Time Polymerase Chain Reaction
Reverse Transcriptase Polymerase Chain Reaction
Tumor Cells, Cultured
Tumor Suppressor Protein p53 / genetics
Tumor Suppressor Protein p53 / metabolism*

Substances

CDKN1A protein, human
Cyclin-Dependent Kinase Inhibitor p21
FOXM1 protein, human
Forkhead Box Protein M1
Forkhead Transcription Factors
Organoplatinum Compounds
RNA, Messenger
RNA, Small Interfering
Reactive Oxygen Species
TP53 protein, human
Tumor Suppressor Protein p53
Oxaliplatin