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Updated: Sep 28, 2025
Author Spotlight: Establishing a Murine Non-Small Cell Lung Cancer Model for Developing Nanoformulations of Anticancer Drugs
Published on: May 10, 2024
A novel NCI-H69V small cell lung cancer functional mini-tumor model for future treatment screening applications
Liezaan van der Merwe1, Hanna Svitina1,2, Clarissa Willers1
1Centre of Excellence for Pharmaceutical Sciences (Pharmacen™), North-West University, Potchefstroom, South Africa.
Abstract:
Small cell lung cancer (SCLC) is aggressive and despite multiple clinical trials, its standard of care is unchanged for the past three decades. In vitro cancer models are crucial in chemotherapy development, and three-dimensional (3D) models aim to bridge the gap between two-dimensional (2D) flat cultures and in vivo testing. Functional 3D spheroids can better represent the in vivo situation and tumor characteristics than 2D models. An NCI-H69V SCLC mini-tumor model was developed in a clinostat-based rotating bioreactor system. Spheroid growth and viability were characterized for 30 days, and the ideal experimental window with mature and metabolically stable spheroids was determined. Application of the model for anticancer treatment screening was validated with the standard chemotherapeutic drug irinotecan, for an exposure period of 72 h. The following parameters were measured: soluble protein content, planar surface area measurements, intracellular adenosine triphosphate and extracellular adenylate kinase levels, and glucose consumption. Histological morphology of the spheroids was observed. The established model proved viable and stable, while treatment with irinotecan caused a decrease in cell growth, viability, and glucose consumption demonstrating reactivity of the model to chemotherapy. Therefore, this NCI-H69V SCLC functional spheroid model could be used for future anticancer compound screening.
Insights
A new 3D spheroid model of small cell lung cancer (SCLC) was developed to improve chemotherapy development. This functional NCI-H69V SCLC model demonstrated responsiveness to irinotecan, showing potential for future anticancer drug screening.
Area of Science:
- Oncology
- Biotechnology
- Cancer Research
Background:
- Small cell lung cancer (SCLC) remains aggressive with an unchanged standard of care for 30 years.
- Three-dimensional (3D) in vitro models offer improved representation of in vivo tumor characteristics compared to 2D cultures.
- Developing advanced cancer models is critical for effective chemotherapy development.
Purpose of the Study:
- To establish and characterize a functional 3D spheroid model of NCI-H69V SCLC.
- To determine the stability and experimental window of the SCLC spheroid model.
- To validate the model's utility for anticancer drug screening using irinotecan.
Main Methods:
- Development of an NCI-H69V SCLC mini-tumor model in a clinostat-based rotating bioreactor.
- Characterization of spheroid growth, viability, and metabolic stability over 30 days.
- Assessment of chemotherapy response using irinotecan, measuring protein content, surface area, ATP, adenylate kinase, and glucose consumption.
Main Results:
- The NCI-H69V SCLC spheroid model demonstrated viability and stability over 30 days.
- Irinotecan treatment led to decreased cell growth, viability, and glucose consumption in the spheroids.
- Histological analysis confirmed spheroid morphology and treatment effects.
Conclusions:
- The established NCI-H69V SCLC functional spheroid model is viable, stable, and chemotherapy-responsive.
- This 3D model holds potential for future anticancer compound screening and drug development in SCLC.
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