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Updated: Aug 6, 2026
A Combined 3D Tissue Engineered In Vitro/In Silico Lung Tumor Model for Predicting Drug Effectiveness in Specific Mutational Backgrounds
Published on: April 6, 2016
2-methoxyestradiol is effective in 2D and 3D models of NCI-H2170 lung squamous cell carcinoma cells
Paul Mellor1, Stephanie Kendall1, Deborah H Anderson1,2,3
1Cancer Research Group, University of Saskatchewan, Saskatoon, Saskatchewan, Canada.
Abstract:
Lung squamous cell carcinoma (LUSC) is a difficult cancer to treat, with few targeted therapies to improve its poor prognosis. The goal of this study was to use a drug repurposing strategy to evaluate and compare drug sensitivities using 2D adherent and 3D spheroid models of NCI-H2170 LUSC cells. Both 2D adherent and 3D spheroid models were used to grow NCI-H2170 lung squamous cell carcinoma cells and evaluate their sensitivity to a large library of food and drug administration (FDA)-approved drugs, including many not typically used as anti-cancer agents. Cell death was assessed in the 2D adherent models, and for the top drugs half maximal effective concentration (EC50) values were determined. For the 3D spheroid models, drugs reducing spheroid size after 4 days of treatment were identified. There were 263 drugs that reduced the cell viability to <20% when cells were grown in 2D in 10 µM drug. When grown in 3D the cells were generally more drug resistant, with 87 drugs capable of reducing spheroid volume when grown over 4 days in 10 µM drug. Interestingly, 60 drugs proved effective in both model systems including many drugs that typically associated with anti-cancer properties. Of these 60, four were further found to have selective effects towards metastatic NCI-H2170 cells as compared to a much less metastatic matched cell line expressing the metastasis suppressor CREB3L1, in both 2D and 3D model systems. These included the hypoxia-inducible factor 1-alpha (HIF-1α inhibitor 2-methoxyestradiol, and three anti-infection agents (cetylpyridinium chloride, chlorhexidine-2HCl, zinc pyrithione).
Conclusions:
These results suggest that the HIF-1α inhibitor 2-methoxyestradiol, and three anti-infection agents (cetylpyridinium chloride, chlorhexidine-2HCl, zinc pyrithione) may be effective for metastatic LUSCs.
Insights
This study repurposed FDA-approved drugs for lung squamous cell carcinoma (LUSC). A hypoxia-inducible factor 1-alpha inhibitor and three anti-infectives showed promise against metastatic LUSC cells.
Area of Science:
- Oncology
- Pharmacology
- Drug Discovery
Background:
- Lung squamous cell carcinoma (LUSC) presents a significant therapeutic challenge with limited targeted treatment options.
- Drug repurposing offers a promising avenue to identify novel anti-cancer agents for LUSC.
Purpose of the Study:
- To evaluate drug sensitivities of NCI-H2170 LUSC cells using 2D and 3D spheroid models.
- To identify FDA-approved drugs, including non-traditional anti-cancer agents, effective against LUSC.
Main Methods:
- Utilized 2D adherent and 3D spheroid cell culture models of NCI-H2170 LUSC cells.
- Screened a large library of FDA-approved drugs for anti-cancer activity.
- Assessed cell death in 2D models and spheroid size reduction in 3D models.
- Determined half maximal effective concentration (EC50) for top-performing drugs.
Main Results:
- 263 drugs reduced viability in 2D models; 87 drugs reduced spheroid volume in 3D models at 10 µM.
- 60 drugs demonstrated efficacy in both 2D and 3D models.
- Four drugs, including a HIF-1α inhibitor and three anti-infectives, selectively targeted metastatic LUSC cells.
Conclusions:
- 2-methoxyestradiol (a HIF-1α inhibitor), cetylpyridinium chloride, chlorhexidine-2HCl, and zinc pyrithione show potential for treating metastatic LUSC.
- These findings support further investigation of these repurposed drugs for LUSC therapy.
