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Updated: Sep 29, 2025
Physiologic Patient Derived 3D Spheroids for Anti-neoplastic Drug Screening to Target Cancer Stem Cells
Published on: July 5, 2019
Microfluidic platform for studying the anti-cancer effect of ursolic acid on tumor spheroid
Shiqi Chang1, Jing Wen1, Yue Su1
1College of Medical Laboratory, Dalian Medical University, Dalian, P. R. China.
Abstract:
At present, the probability that a new anti-tumor drug will eventually succeed in clinical trials is extremely low. In order to make up for this shortcoming, the use of a three-dimensional (3D) cell culture model for secondary screening is often necessary. Cell spheroid is the easiest 3D model tool for drug screening. In this study, the microfluidic chip with a microwell array was manufactured, which could allow the formation of tumor spheroids with uniform size and easily retrieve cell spheroids from the chip. Cell spheroids were successfully cultured for over 15 days and the survival rate was as high as 80%. Subsequently, cellular response to the ursolic acid (UA) was observed on the chip. Compared to the monolayer culture cells in vitro, the tumor spheroids showed minor levels of epithelial-mesenchymal transition fluctuation after drug treatment. The mechanism of cell spheroid resistance to UA was further verified by detecting the expression level of upstream pathway proteins. But the invasive ability of tumor spheroids was attenuated when the duration of action of UA extended. The anti-cancer effect of UA was innovatively evaluated on breast cancer by using the microfluidic device, which could provide a basis and direction for future preclinical research on UA.
Insights
This study developed a microfluidic device for creating uniform tumor spheroids, improving anti-cancer drug screening. The device demonstrated ursolic acid
Area of Science:
- Biomedical Engineering
- Cancer Research
- Drug Development
Background:
- The low success rate of anti-tumor drugs in clinical trials necessitates improved preclinical screening methods.
- Three-dimensional (3D) cell culture models, particularly cell spheroids, offer a more physiologically relevant platform for drug evaluation.
- Existing methods for spheroid culture and analysis can be cumbersome and lack uniformity.
Purpose of the Study:
- To develop and validate a microfluidic device for uniform tumor spheroid formation and drug screening.
- To investigate the response of breast cancer spheroids to ursolic acid (UA) using the developed microfluidic system.
- To elucidate the mechanisms underlying spheroid resistance and UA efficacy in a 3D cancer model.
Main Methods:
- Fabrication of a microfluidic chip with a microwell array for controlled spheroid formation.
- Long-term culture (over 15 days) of tumor spheroids with high survival rates (80%).
- Assessment of cellular response, epithelial-mesenchymal transition (EMT), and protein expression in response to ursolic acid (UA) treatment within the microfluidic device.
Main Results:
- Uniform tumor spheroids were successfully generated and cultured for extended periods on the microfluidic chip.
- Tumor spheroids exhibited less epithelial-mesenchymal transition fluctuation compared to monolayer cultures upon UA treatment.
- The invasive ability of tumor spheroids was reduced with prolonged UA exposure, indicating a time-dependent anti-cancer effect.
Conclusions:
- The microfluidic device provides an effective platform for generating uniform tumor spheroids for enhanced drug screening.
- Ursolic acid demonstrates anti-cancer effects on breast cancer spheroids, with mechanisms involving EMT modulation and invasiveness reduction.
- This approach offers a valuable preclinical research tool for evaluating anti-cancer agents like UA.
