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Original Research ARTICLE Provisionally accepted The full-text will be published soon. Notify me

Front. Oncol. | doi: 10.3389/fonc.2019.00153

Assessing Radiosensitivity of Bladder Cancer In Vitro: A 2D vs 3D Approach

  • 1Department of Radiation Oncology, American University of Beirut Medical Center, Lebanon
  • 2Department of Anatomy, Cell Biology and Physiological Sciences, Faculty of Medicine, American University of Beirut, Lebanon

Background: Bladder cancer is the fourth most commonly diagnosed cancer among males worldwide. Current treatment strategies established for bladder cancer mainly consist of cystectomy yet advances in radiation therapy have pointed to the value of organ-preserving strategies in preserving patients’ quality of life.
Aim: To study and compare the radiosensitivity in two-dimension (2D) and physiologically-relevant three-dimension (3D) in vitro culture of 3 human bladder cancer cell lines, RT4, T24 and UM-UC-3.
Materials and methods: Clonogenic assay was performed to assess cells’ radiosensitivity in 2D. Employing the 3D MatrigelTM-based cultures to enrich for cancer stem cells (CSCs) allowed us to assess the survival of this subpopulation of cells via evaluating the number, i.e. sphere forming unit (SFU), and the sizes of cultured spheres, formed from cells exposed to different radiation doses compared to non-irradiated cells.
Results: Irradiating cells with increasing radiation doses revealed highest survival rates with RT4 cells in 2D, followed by T24 and UM-UC-3. In 3D, however, UM-UC-3 cells were shown to be the most radio-resistant as evidenced by the number of spheres formed, yet they displayed the least efficient volume reduction/regression (VR), whilst the volume decreased significantly for both RT4 and T24 cells. Sphere VR and sphere ratio (SR) values were then plotted against each other demonstrating a linear correlation between volume and number with RT4 and UM-UC-3 cell lines, but not T24. Lastly, multiple regression model was employed to evaluate the possibility of obtaining a function combining both 3D parameters, SR and VR, with the surviving fraction (SF) in 2D, and showed a linear regression for T24 cells only, with a correlation coefficient of 0.97 for the combined parameters.
Conclusion: We were able to radiobiologically characterize 3 human bladder cancer cell lines showing differential effects of radiation between 2D and 3D culture systems, paving the way for achieving better assessment of radiosensitivity of bladder cancer in vitro.

Keywords: Bladder cancer, radiosensitivity, radioresistance, cancer stem cells, modelling

Received: 18 Sep 2018; Accepted: 22 Feb 2019.

Edited by:

Fabio Grizzi, Humanitas Research Hospital, Italy

Reviewed by:

Felix K. Chun, University Medical Center Hamburg-Eppendorf, Germany
Hiroaki Matsumoto, Yamaguchi University, Japan
Arjola Qehajaj, University Medical Center Mother Teresa (QSUT), Albania  

Copyright: © 2019 Bodgi, Bahmad, Araji, Al Choboq, Bou-Gharios, Cheaito, Zeidan, Eid, Geara and Abou-Kheir. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.

* Correspondence: PhD. Wassim Abou-Kheir, Department of Anatomy, Cell Biology and Physiological Sciences, Faculty of Medicine, American University of Beirut, Beirut, Lebanon,