Vesnarinone downregulates CXCR4 expression via upregulation of Krüppel-like factor 2 in oral cancer cells

Daisuke Uchida, Tomitaro Onoue, Nasima Mila Begum, Nobuyuki Kuribayashi, Yoshifumi Tomizuka, Tetsuya Tamatani, Hirokazu Nagai, Youji Miyamoto

Research output: Contribution to journalArticlepeer-review

35 Citations (Scopus)

Abstract

Background: We have demonstrated that the stromal cell-derived factor-1 (SDF-1; CXCL12)/CXCR4 system is involved in the establishment of lymph node metastasis in oral squamous cell carcinoma (SCC). Chemotherapy is a powerful tool for the treatment of oral cancer, including oral SCC; however, the effects of chemotherapeutic agents on the expression of CXCR4 are unknown. In this study, we examined the expression of CXCR4 associated with the chemotherapeutic agents in oral cancer cells. Results: The expression of CXCR4 was examined using 3 different chemotherapeutic agents; 5-fluorouracil, cisplatin, and vesnarinone (3,4-dihydro-6-[4-(3,4-dimethoxybenzoyl)-1-piperazinyl]-2-(1H) -quinolinone) in B88, a line of oral cancer cells that exhibits high levels of CXCR4 and lymph node metastatic potential. Of the 3 chemotherapeutic agents that we examined, only vesnarinone downregulated the expression of CXCR4 at the mRNA as well as the protein level. Vesnarinone significantly inhibited lymph node metastasis in tumor-bearing nude mice. Moreover, vesnarinone markedly inhibited 2.7-kb human CXCR4 promoter activity, and we identified the transcription factor, Krüppel-like factor 2 (KLF2), as a novel vesnarinone-responsive molecule, which was bound to the CXCR4 promoter at positions -300 to -167 relative to the transcription start site. The forced-expression of KLF2 led to the downregulation of CXCR4 mRNA and impaired CXCR4 promoter activity. The use of siRNA against KLF2 led to an upregulation of CXCR4 mRNA. Conclusion: These Results indicate that vesnarinone downregulates CXCR4 via the upregulation of KLF2 in oral cancer.

Original languageEnglish
Article number62
JournalMolecular Cancer
Volume8
DOIs
Publication statusPublished - 2009 Aug 12

ASJC Scopus subject areas

  • Molecular Medicine
  • Oncology
  • Cancer Research

Fingerprint Dive into the research topics of 'Vesnarinone downregulates CXCR4 expression via upregulation of Krüppel-like factor 2 in oral cancer cells'. Together they form a unique fingerprint.

Cite this