Nickel chloride administration prevents the growth of oral squamous cell carcinoma

Abstract

The effect of NiCl₂ on oral squamous cell carcinoma-derived cell line HSC3 was examined. Incubation with 1 mM NiCl₂ significantly reduced the expression of MMPs at mRNA and protein levels. The in vivo orthotopic implantation model was established by injecting highly metastatic subcell line HSC3-M3 to nude mouse tongue. After 1 week of injection, mice were fed with or without 1 mM NiCl₂-containing water for two to three weeks. Immunohistochamical examination revealed that MMP9 expression was drastically reduced in NiCl2-fed mice. By CT images, cancer mass was observed as a translucent area in control mice. In NiCl₂-fed mice, much highly translucent area was observed within the translucent area. Histologically, this area corresponded to the necrotic area in the tumor mass. Real-time PCR analysis revealed the reduced expression of angiogenic factors such as IL-8 and VEGF mRNA in NiCl₂-fed mice. To further examine the effect of NiCl₂ on metastasis, human β-globin gene expression in regional lymphnodes was compared. The β-globin gene was totaly absent in NiCl₂-fed mice. Moreover, various cancer metastasis-related genes were inhibited in NiCl₂-fed mice by PCR array analysis. The results indicated that NiCl₂ might be a promising new anti-cancer therapeutics for the oral cancer treatment.