AI Insight
Researchers tested a library of FDA-approved drugs on NCI-H2170 lung squamous cell carcinoma cells grown in both traditional 2D cultures and more realistic 3D spheroid models. Of 263 drugs effective in 2D, only 87 reduced tumor size in 3D models, with 60 drugs working in both systems. Four drugs showed selective effectiveness against metastatic cells compared to non-metastatic cells: the HIF-1α inhibitor 2-methoxyestradiol and three anti-infection agents (cetylpyridinium chloride, chlorhexidine-2HCl, and zinc pyrithione).
Why it matters
This drug repurposing approach identifies existing FDA-approved compounds that could potentially be repositioned to treat lung squamous cell carcinoma, a cancer with limited treatment options and poor prognosis. The finding that common anti-infection agents show anti-cancer properties against metastatic cells could accelerate clinical testing since these drugs already have established safety profiles.
Understand the Science
by Paul Mellor, Stephanie Kendall, Deborah H. Anderson
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.
Source: 2-methoxyestradiol is effective in 2D and 3D models of NCI-H2170 lung squamous cell carcinoma cells