Vesnarinone downregulates CXCR4 expression via upregulation of Krüppel-like factor 2 in oral cancer cellsReport as inadecuate




Vesnarinone downregulates CXCR4 expression via upregulation of Krüppel-like factor 2 in oral cancer cells - Download this document for free, or read online. Document in PDF available to download.

Molecular Cancer

, 8:62

First Online: 12 August 2009Received: 21 April 2009Accepted: 12 August 2009

Abstract

BackgroundWe 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.

ResultsThe 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.

ConclusionThese Results indicate that vesnarinone downregulates CXCR4 via the upregulation of KLF2 in oral cancer.

AbbreviationsOSCCoral squamous cell carcinoma

SDF-1stromal cell-derived factor-1; vesnarinone; 3,4-dihydro-6-4-3,4-dimethoxybenzoyl-1-piperazinyl-2-1H-quinolinone

CMCcarboxymethylcellulose

5-FU5-fluorouracil

CDDPcis-diamminedichloroplatinum

DMEMDulbecco-s modified Eagle medium

GAPDHglyceraldehyde 3-phosphate dehydrogenase.

Electronic supplementary materialThe online version of this article doi:10.1186-1476-4598-8-62 contains supplementary material, which is available to authorized users.

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Author: Daisuke Uchida - Tomitaro Onoue - Nasima-Mila Begum - Nobuyuki Kuribayashi - Yoshifumi Tomizuka - Tetsuya Tamatani - Hirokaz

Source: https://link.springer.com/







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