On-chip combined radiotherapy and chemotherapy testing on soft-tissue sarcoma spheroids to study cell death using flow cytometry and clonogenic assay
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 socia...
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| Veröffentlicht in: | Scientific reports 2019-02, Vol.9 (1), p.2214-2214, Article 2214 |
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| creator | Patra, Bishnubrata Lafontaine, Julie Bavoux, Maeva Zerouali, Karim Glory, Audrey Ahanj, Mohsen Carrier, Jean-François Gervais, Thomas Wong, Philip |
| description | 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 µM and 20 µM. The spheroids culture chambers within the device were arranged in a 3 × 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. |
| doi_str_mv | 10.1038/s41598-019-38666-9 |
| format | Article |
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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 µM and 20 µM. The spheroids culture chambers within the device were arranged in a 3 × 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.</description><identifier>ISSN: 2045-2322</identifier><identifier>EISSN: 2045-2322</identifier><identifier>DOI: 10.1038/s41598-019-38666-9</identifier><identifier>PMID: 30778138</identifier><language>eng</language><publisher>London: Nature Publishing Group UK</publisher><subject>13/106 ; 13/31 ; 13/62 ; 14/63 ; 631/61/32 ; 631/67/1059/485 ; Apoptosis ; Cell culture ; Cell death ; Chemotherapy ; Doxorubicin ; Drug discovery ; Drug screening ; Flow cytometry ; Humanities and Social Sciences ; Microfluidics ; multidisciplinary ; p53 Protein ; Patients ; Radiation therapy ; Sarcoma ; Science ; Science (multidisciplinary) ; Spheroids ; Tissues ; Tumors</subject><ispartof>Scientific reports, 2019-02, Vol.9 (1), p.2214-2214, Article 2214</ispartof><rights>The Author(s) 2019</rights><rights>This work is published under http://creativecommons.org/licenses/by/4.0/ (the “License”). Notwithstanding the ProQuest Terms and Conditions, you may use this content in accordance with the terms of the License.</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c474t-948b0809e0ca19eab68579fcc28e1ba05233730d24283ef1f1736876798cff513</citedby><cites>FETCH-LOGICAL-c474t-948b0809e0ca19eab68579fcc28e1ba05233730d24283ef1f1736876798cff513</cites><orcidid>0000-0002-2025-9082 ; 0000-0002-7761-0283</orcidid></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC6379442/pdf/$$EPDF$$P50$$Gpubmedcentral$$Hfree_for_read</linktopdf><linktohtml>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC6379442/$$EHTML$$P50$$Gpubmedcentral$$Hfree_for_read</linktohtml><link.rule.ids>230,314,727,780,784,864,885,27924,27925,41120,42189,51576,53791,53793</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/30778138$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Patra, Bishnubrata</creatorcontrib><creatorcontrib>Lafontaine, Julie</creatorcontrib><creatorcontrib>Bavoux, Maeva</creatorcontrib><creatorcontrib>Zerouali, Karim</creatorcontrib><creatorcontrib>Glory, Audrey</creatorcontrib><creatorcontrib>Ahanj, Mohsen</creatorcontrib><creatorcontrib>Carrier, Jean-François</creatorcontrib><creatorcontrib>Gervais, Thomas</creatorcontrib><creatorcontrib>Wong, Philip</creatorcontrib><title>On-chip combined radiotherapy and chemotherapy testing on soft-tissue sarcoma spheroids to study cell death using flow cytometry and clonogenic assay</title><title>Scientific reports</title><addtitle>Sci Rep</addtitle><addtitle>Sci Rep</addtitle><description>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 µM and 20 µM. The spheroids culture chambers within the device were arranged in a 3 × 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.</description><subject>13/106</subject><subject>13/31</subject><subject>13/62</subject><subject>14/63</subject><subject>631/61/32</subject><subject>631/67/1059/485</subject><subject>Apoptosis</subject><subject>Cell culture</subject><subject>Cell death</subject><subject>Chemotherapy</subject><subject>Doxorubicin</subject><subject>Drug discovery</subject><subject>Drug screening</subject><subject>Flow cytometry</subject><subject>Humanities and Social Sciences</subject><subject>Microfluidics</subject><subject>multidisciplinary</subject><subject>p53 Protein</subject><subject>Patients</subject><subject>Radiation therapy</subject><subject>Sarcoma</subject><subject>Science</subject><subject>Science (multidisciplinary)</subject><subject>Spheroids</subject><subject>Tissues</subject><subject>Tumors</subject><issn>2045-2322</issn><issn>2045-2322</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2019</creationdate><recordtype>article</recordtype><sourceid>C6C</sourceid><sourceid>ABUWG</sourceid><sourceid>AFKRA</sourceid><sourceid>AZQEC</sourceid><sourceid>BENPR</sourceid><sourceid>CCPQU</sourceid><sourceid>DWQXO</sourceid><sourceid>GNUQQ</sourceid><recordid>eNp9kc1u1DAUhSMEolXpC7BAltiwcfFPEtsbJFTxU6lSN7C2HMeZuErs4OuA8iC8L57OMBQWeGPL97vn-vhU1UtKrijh8i3UtFESE6owl23bYvWkOmekbjDjjD19dD6rLgHuSVkNUzVVz6szToSQlMvz6uddwHb0C7Jx7nxwPUqm9zGPLpllQyb0yI5uPl1kB9mHHYoBQRwyzh5gdQhMKgIGwVK46HtAOSLIa78h66YJ9c7kEa2wbx2m-APZLcfZ5XQcMcUQdy54iwyA2V5UzwYzgbs87hfV148fvlx_xrd3n26u399iW4s6Y1XLjkiiHLGGKme6VjZCDdYy6Whnil_OBSc9q5nkbqADFbyVohVK2mFoKL-o3h10l7WbXW9dyMlMekl-NmnT0Xj9dyX4Ue_id91yoeqaFYE3R4EUv63lb_TsYe_YBBdX0IxK3jZEkKagr_9B7-OaQrH3QFEhJd9T7EDZFAGSG06PoUTvg9eH4HUJXj8Er1VpevXYxqnld8wF4AcASinsXPoz-z-yvwDQJ7yk</recordid><startdate>20190218</startdate><enddate>20190218</enddate><creator>Patra, Bishnubrata</creator><creator>Lafontaine, Julie</creator><creator>Bavoux, Maeva</creator><creator>Zerouali, Karim</creator><creator>Glory, Audrey</creator><creator>Ahanj, Mohsen</creator><creator>Carrier, Jean-François</creator><creator>Gervais, Thomas</creator><creator>Wong, Philip</creator><general>Nature Publishing Group UK</general><general>Nature Publishing Group</general><scope>C6C</scope><scope>NPM</scope><scope>AAYXX</scope><scope>CITATION</scope><scope>3V.</scope><scope>7X7</scope><scope>7XB</scope><scope>88A</scope><scope>88E</scope><scope>88I</scope><scope>8FE</scope><scope>8FH</scope><scope>8FI</scope><scope>8FJ</scope><scope>8FK</scope><scope>ABUWG</scope><scope>AFKRA</scope><scope>AZQEC</scope><scope>BBNVY</scope><scope>BENPR</scope><scope>BHPHI</scope><scope>CCPQU</scope><scope>DWQXO</scope><scope>FYUFA</scope><scope>GHDGH</scope><scope>GNUQQ</scope><scope>HCIFZ</scope><scope>K9.</scope><scope>LK8</scope><scope>M0S</scope><scope>M1P</scope><scope>M2P</scope><scope>M7P</scope><scope>PIMPY</scope><scope>PQEST</scope><scope>PQQKQ</scope><scope>PQUKI</scope><scope>Q9U</scope><scope>7X8</scope><scope>5PM</scope><orcidid>https://orcid.org/0000-0002-2025-9082</orcidid><orcidid>https://orcid.org/0000-0002-7761-0283</orcidid></search><sort><creationdate>20190218</creationdate><title>On-chip combined radiotherapy and chemotherapy testing on soft-tissue sarcoma spheroids to study cell death using flow cytometry and clonogenic assay</title><author>Patra, Bishnubrata ; 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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 µM and 20 µM. The spheroids culture chambers within the device were arranged in a 3 × 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.</abstract><cop>London</cop><pub>Nature Publishing Group UK</pub><pmid>30778138</pmid><doi>10.1038/s41598-019-38666-9</doi><tpages>1</tpages><orcidid>https://orcid.org/0000-0002-2025-9082</orcidid><orcidid>https://orcid.org/0000-0002-7761-0283</orcidid><oa>free_for_read</oa></addata></record> |
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| subjects | 13/106 13/31 13/62 14/63 631/61/32 631/67/1059/485 Apoptosis Cell culture Cell death Chemotherapy Doxorubicin Drug discovery Drug screening Flow cytometry Humanities and Social Sciences Microfluidics multidisciplinary p53 Protein Patients Radiation therapy Sarcoma Science Science (multidisciplinary) Spheroids Tissues Tumors |
| title | On-chip combined radiotherapy and chemotherapy testing on soft-tissue sarcoma spheroids to study cell death using flow cytometry and clonogenic assay |
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