Nickel chloride administration prevents the growth of oral squamous cell carcinoma

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. Realtime 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.