Nickel chloride administration prevents the growth of oral squamous cell carcinoma
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Hirotaka Ota1,2,*, Takashi Shionome3,*, Hisashi Suguro4,5, Satsuki Saito6, Kosuke Ueki6, Yoshinori Arai7 and Masatake Asano1,2
1Department of Pathology, Nihon University School of Dentistry, Tokyo, Japan
2Division of Immunology and Pathobiology, Nihon University School of Dentistry, Tokyo, Japan
3Department of Partial Denture Prosthodontics, Nihon University School of Dentistry, Tokyo, Japan
4Department of Endodontics, Nihon University School of Dentistry, Tokyo, Japan
5Division of Advanced Dental Treatment, Dental Research Center, Nihon University School of Dentistry, Tokyo, Japan
6Division of Applied Oral Sciences, Nihon University Graduate School of Dentistry, Tokyo, Japan
7Nihon University School of Dentistry, Tokyo, Japan
*These authors contributed equally to this work
Masatake Asano, email: [email protected]
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
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.
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