Nickel chloride administration prevents the growth of oral squamous cell carcinoma

// Hirotaka Ota 1, 2, * , Takashi Shionome 3, * , Hisashi Suguro 4, 5 , Satsuki Saito 6 , Kosuke Ueki 6 , Yoshinori Arai 7 and Masatake Asano 1, 2 1 Department of Pathology, Nihon University School of Dentistry, Tokyo, Japan 2 Division of Immunology and Pathobiology, Nihon University School of Dentistry, Tokyo, Japan 3 Department of Partial Denture Prosthodontics, Nihon University School of Dentistry, Tokyo, Japan 4 Department of Endodontics, Nihon University School of Dentistry, Tokyo, Japan 5 Division of Advanced Dental Treatment, Dental Research Center, Nihon University School of Dentistry, Tokyo, Japan 6 Division of Applied Oral Sciences, Nihon University Graduate School of Dentistry, Tokyo, Japan 7 Nihon University School of Dentistry, Tokyo, Japan * These authors contributed equally to this work Correspondence to: Masatake Asano, email: asano.masatake@nihon-u.ac.jp Keywords: nickel chloride; oral squamous cell carcinoma; matrix metalloproteinase; nude mouse; nuclear factor-kappa B Received: April 27, 2017      Accepted: September 03, 2017      Published: May 08, 2018 ABSTRACT The effect of NiCl 2 on oral squamous cell carcinoma-derived cell line HSC3 was examined. Incubation with 1 mM NiCl 2 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 NiCl 2 -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 NiCl 2 -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 NiCl 2 -fed mice. To further examine the effect of NiCl 2 on metastasis, human β-globin gene expression in regional lymphnodes was compared. The β-globin gene was totaly absent in NiCl 2 -fed mice. Moreover, various cancer metastasis-related genes were inhibited in NiCl 2 -fed mice by PCR array analysis. The results indicated that NiCl 2 might be a promising new anti-cancer therapeutics for the oral cancer treatment.