3D cell cultures exhibit increased drug resistance, particularly to taxanes.

person Chiara Maestri SageMedic Corp., Redwood City, CA info_outline Chiara Maestri, Jahanvi Kumar, Rajeshwar Nitiyanandan, Ivan Trus, Ricardo Parker, Brigitte Apfel, Christian Apfel

Authors person Chiara Maestri SageMedic Corp., Redwood City, CA info_outline Chiara Maestri, Jahanvi Kumar, Rajeshwar Nitiyanandan, Ivan Trus, Ricardo Parker, Brigitte Apfel, Christian Apfel Organizations SageMedic Corp., Redwood City, CA Abstract Disclosures Research Funding No funding sources reported Background: Cell culture platforms could be categorized into two main types: 2D and 3D. 3D cell cultures, known for mimicking the physiological cellular environment, are commonly preferred by researchers to assess drug responses as they accurately reproduce aspects of the in vivo cell behavior. We hypothesized that dose-response curves of 2D and 3D platforms may be drug dependent, with some being more sensitive or resistant depending on the platform. Methods: MCF-7 cancer cells were cultured and plated using a 2D flat bottom well plate platform or using a matrix-based and a matrix-free 3D platform. Cells were treated with chemotherapies and targeted therapies for four days and cellular sensitivity was assessed through a viability assay. Four-parameter logistic (4PL) dose response curves were generated and IC 50 values (µM/C max ) were quantified to understand the differences in dose response curves between the 2D and 3D cellular platforms. Results: While the dose-response curves generally correlate between 2D vs. 3D matrix-based (r2=0.82, p<0.001) and 2D vs. 3D matrix-free methods (r2=0.78, p<0.001), noteworthy variations were observed for certain drugs, particularly paclitaxel (2D IC50= 66; 3D matrix-based IC50 = ≥100; 3D matrix-free IC50 = ≥100) and docetaxel (2D IC50 = ≥34; 3D matrix-based IC50 = ≥100; 3D matrix-free IC50 = ≥100). Additionally, a general increase in resistance was evident when cells formed 3D structures compared to the 2D monolayer condition, as indicated by regression analysis (Y-intercept = 0.55, CI95% 0.32 to 0.78; slope = 0.47, CI95% 0.20 to 0.75). Conclusions: Our findings reveal that taxanes such as paclitaxel and docetaxel exhibit distinctive resistance patterns in 3D structures. In addition, a substantial increase in cellular resistance is observed in 3D cellular models when compared to the 2D assay for most drugs. Despite the overall correlation, these drug-specific differences should be considered. Thus, the next generation of an extreme drug resistance assay, aimed at enhancing the quality of life for patients by avoiding ineffective therapies, might preferentially employ a 3D platform to tailor patients’ cancer therapies.

Pre-clinical