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Updated: Feb 9, 2026

Modeling Oral-Esophageal Squamous Cell Carcinoma in 3D Organoids
Published on: December 23, 2022
Nickel chloride administration prevents the growth of oral squamous cell carcinoma
Hirotaka Ota1,2, Takashi Shionome3, Hisashi Suguro4,5
1Department of Pathology, Nihon University School of Dentistry, Tokyo, Japan.
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.
Insights
Nickel chloride (NiCl2) significantly inhibited oral cancer progression and metastasis in preclinical models. NiCl2 reduced tumor growth, induced necrosis, and suppressed key genes involved in angiogenesis and cancer spread.
Area of Science:
- Oncology
- Biochemistry
- Molecular Biology
Background:
- Oral squamous cell carcinoma (OSCC) is a significant global health concern.
- Metastasis is a primary driver of mortality in OSCC.
- Novel therapeutic strategies are needed to improve OSCC treatment outcomes.
Purpose of the Study:
- To investigate the anti-cancer effects of nickel chloride (NiCl2) on OSCC.
- To evaluate the impact of NiCl2 on tumor growth, angiogenesis, and metastasis in vivo.
- To explore the potential of NiCl2 as a therapeutic agent for oral cancer.
Main Methods:
- In vitro studies using the HSC3 OSCC cell line to assess MMP expression.
- In vivo orthotopic implantation model in nude mice using the HSC3-M3 subline.
- Treatment with NiCl2-containing water in mice.
- Immunohistochemistry, CT imaging, real-time PCR, and PCR array analysis to evaluate tumor characteristics and gene expression.
Main Results:
- NiCl2 significantly reduced matrix metalloproteinase (MMP) expression at both mRNA and protein levels.
- In vivo, NiCl2 treatment led to reduced tumor mass, increased necrosis, and suppressed expression of angiogenic factors (IL-8, VEGF).
- NiCl2 administration completely inhibited human beta-globin gene expression in lymph nodes, indicating a blockade of metastasis. Gene expression analysis revealed inhibition of various metastasis-related genes.
Conclusions:
- NiCl2 demonstrates potent anti-cancer properties against oral squamous cell carcinoma.
- NiCl2 effectively inhibits tumor growth, angiogenesis, and metastasis.
- NiCl2 represents a promising therapeutic candidate for oral cancer treatment.
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