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Medical Molecular Morphology

, Volume 45, Issue 2, pp 91–97 | Cite as

Effects of CRM197, a specific inhibitor of HB-EGF, in oral cancer

  • Suguru Dateoka
  • Yuichi Ohnishi
  • Kenji Kakudo
Original Paper

Abstract

CRM197, a nontoxic mutant of diphtheria toxin, is a specific inhibitor of heparin-binding epidermal growth factor (EGF)-like growth factor (HB-EGF), which belongs to the EGF family that has been implicated in the increased progression, proliferation, and metastasis of oral cancer. In this study, we analyzed the antitumor effects of CRM197, which represent possible chemotherapeutic agents for oral cancer. In the experiment, we used the oral squamous cell carcinoma cell lines HSC3 and SAS. Cells treated with CRM197 were analyzed based on cell viability, MTT assay, invasion assay, Western blot, and zymography. HSC3 cells were injected subcutaneously into female BALB/c nu/nu mice at 5 weeks of age. CRM197 and/or CDDP were injected intraperitoneally into tumor-bearing mice, and tumor volume was measured over time. HB-EGF expression in HSC3 and SAS cells treated with CRM197 was significantly reduced and cell proliferation was inhibited. The invasiveness of CRM197-treated cells was relatively low. MMP-9 and VEGF were suppressed in HSC3 treated with CRM197 on zymography and Western blot. Further, tumor growth in xenografted mice was suppressed by CRM197 or CDDP at 1 mg/kg/day. Also, the coadministration of CDDP and CRM197 at 1 mg/kg/day completely inhibited tumor formation. These results suggest that HB-EGF is a target for oral cancer and that CRM197 is effective in oral cancer therapy.

Key words

Heparin-binding epidermal growth factor Squamous cell carcinoma Matrix metalloproteinase 9 CRM197 CDDP Chemotherapy 

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Copyright information

© The Japanese Society for Clinical Molecular Morphology 2012

Authors and Affiliations

  1. 1.Second Department of Oral and Maxillofacial Surgery, Graduate School of DentistryOsaka Dental UniversityOsakaJapan
  2. 2.Second Department of Oral and Maxillofacial SurgeryOsaka Dental UniversityOsakaJapan

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