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On-chip combined radiotherapy and chemotherapy testing on soft-tissue sarcoma spheroids to study cell death using flow cytometry and clonogenic assay

Bishnubrata Patra, Julie Lafontaine, Maeva Bavoux, Karim Zerouali, Audrey Glory, Mohsen Ahanj, Jean-François Carrier, Thomas Gervais, Philip Wong

Article (2019)

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Abstract

Radiotherapy (RT) and chemotherapy (CT) are the major therapeutics to treat cancer patients. Conventional in vitro 2D models are insufficient to study the combined effects of RT and CT towards optimized dose selection or drug screening. Soft-tissue sarcomas (STS) are rare cancers with profound social impacts as they affect patients of all ages. We developed a microfluidic device to form and culture STS spheroids to study the combined cytotoxicities of RT and CT. Uniformly-sized spheroids of two different cell lines, STS 93 and STS 117, were formed in the device. RT doses of 0.5 Gy, 2 Gy, and 8 Gy were used in combination with CT, doxorubicin at 2 microM and 20 microM. The spheroids culture chambers within the device were arranged in a 3 x 5 matrix form. The device was made "peelable", which enabled us to collect spheroids from each treatment condition separately. Collected spheroids were dissociated into single cells and evaluated using flow cytometry and clonogenic assays. Through this workflow, we observed that STS 93 spheroids treated with doxorubicin die through apoptosis, whereas RT induced death through other pathways. Spheroids from the p53 mutant STS 117 cell line were more resistant to RT and doxorubicin. The developed device could be used for the discovery of new drugs and RT synergies.
Subjects: 1900 Biomedical engineering > 1900 Biomedical engineering
3100 Physics > 3100 Physics
6400 Life sciences research related to human health and disease > 6400 Life sciences research related to human health and disease
Department: Department of Engineering Physics
Institut de génie biomédical
Research Center: Other
Funders: Cancer Research Society, Institut du Cancer de Montréal, Mitacs, Fonds de Recherche du Québec – Santé, Natural Sciences and Engineering Council of Canada, Canada First Research Excellence Fund
Grant number: 20276, IT05953, 32730, 34612
PolyPublie URL: https://publications.polymtl.ca/5079/
Journal Title: Scientific Reports (vol. 9, no. 1)
Publisher: Nature
DOI: 10.1038/s41598-019-38666-9
Official URL: https://doi.org/10.1038/s41598-019-38666-9
Date Deposited: 04 Aug 2022 14:41
Last Modified: 10 Nov 2022 16:04
Cite in APA 7: Patra, B., Lafontaine, J., Bavoux, M., Zerouali, K., Glory, A., Ahanj, M., Carrier, J.-F., Gervais, T., & Wong, P. (2019). On-chip combined radiotherapy and chemotherapy testing on soft-tissue sarcoma spheroids to study cell death using flow cytometry and clonogenic assay. Scientific Reports, 9(1), 2214 (9 pages). https://doi.org/10.1038/s41598-019-38666-9

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