Author(s): Isaac Packer, Jeffery Okojie, Delany Anderson, Victoria Johnson, Paytin Curran
Mentor(s): Jared Barrott
Institution BYU
Background: Cancer drug screening is commonly performed on two-dimensional (2D) cancer cell lines. Recent innovations in cell line development and methods of incubation has led to further interest in the development of three-dimensional (3D) organoids from standard cancer cell lines and patient-derived tissue. Our research intends to test the relationship between cell viability of 2D cancer cell lines and the viability of 3D organoids during cancer drug screening. Despite the same origination of the cells we hypothesize that the 3D cancer models will differentially respond to a panel of 131 FDA approved drugs. Methods: Our research involves placing 2D cell lines into an innovative gravity free environment to simultaneously create 3D organoids along with the 2D cell lines. We performed both an MTT assay to assess cell viability of both the 2D cells and the cells in the 3D organoids with changing concentrations of the chosen drug. Along with the MTT assay, a Cell Titer Glo assay was performed to further determine cell viability via ATP prevalence after cell lysis of the 2D and 3D organoid cells affected by the same varying drug concentrations. Results: In a synovial sarcoma cell line we applied the standard of care chemotherapy doxorubicin, and analyzed cell viability. We grew the 3D organoids in three different methods and showed differential responses depending on the method. The most relevant models are the models with increased perfusion and they demonstrated the least sensitivity. 3D organoids grown in the gravity-free environment showed a forty-fold decrease in sensitivity in the 3D organoids when compared to the 2D cells via analysis of a Cell Titer Glo assay. Discussion: As we continue to test more cell lines with different drugs from the FDA panel we expect to see further results supporting this decreased sensitivity.