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Anastasov, N. ; Höfig, I. ; Radulovic, V. ; Strobel, S.* ; Salomon, M.* ; Lichtenberg, J.* ; Rothenaigner, I. ; Hadian, K. ; Kelm, J.M.* ; Thirion, C.* ; Atkinson, M.J.

A 3D-microtissue-based phenotypic screening of radiation resistant tumor cells with synchronized chemotherapeutic treatment.

BMC Cancer 15:466 (2015)
Publ. Version/Full Text DOI
Open Access Gold
Creative Commons Lizenzvertrag
BACKGROUND: Radiation resistance presents a challenge to the effective treatment of cancer. If therapeutic compounds were capable of resensitizing resistant tumours then a concurrent chemo-radiation treatment could be used to overcome radiation resistance. METHODS: We have developed a phenotypic assay to investigate the response of radiation resistant breast cancer cells grown in 3D-microtissue spheroids to combinations of radiation and established chemotherapeutic drugs. The effects were quantified by real time high content imaging of GFP detection area over 14 days. Ten established chemotherapeutic drugs were tested for their ability to enhance the effects of radiation. RESULTS: Of ten analysed chemotherapeutics, vinblastine was the most effective compound, with docetaxel and doxorubicine being less effective in combination with radiation. To investigate the response in a model closer to the in vivo situation we investigated the response of heterotypic 3D microtissues containing both fibroblasts and breast cancer cells. Drug treatment of these heterotypic 3D cultures confirmed treatment with radiation plus vinblastine to be additive in causing breast cancer growth inhibition. We have validated the screen by comparing radiation sensitizing effects of known chemotherapeutic agents. In both monotypic and heterotypic models the concurrent treatment of vinblastine and radiation proved more effective inhibitors of mammary cancer cell growth. The effective concentration range of both vinblastine and radiation are within the range used in treatment, suggesting the 3D model will offer a highly relevant screen for novel compounds. CONCLUSIONS: For the first time comfortable 3D cell-based phenotypic assay is available, that allows high throughput screening of compounds with radiation therapy modulating capacity, opening the field to drug discovery.
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Publication type Article: Journal article
Document type Scientific Article
Keywords 3d-microtissues ; High Content Screen (hcs) ; Potentiating Drugs ; Radiation Therapy ; Tumor Growth ; Vinblastine; Metastatic Breast-cancer; Phase-iii Trial; Lung-cancer; Line Chemotherapy; Anticancer Agents; Paclitaxel Taxol; Gamma-radiation; 3d; Docetaxel; Therapy
ISSN (print) / ISBN 1471-2407
e-ISSN 1471-2407
Journal BMC Cancer
Quellenangaben Volume: 15, Issue: 1, Pages: , Article Number: 466 Supplement: ,
Publisher BioMed Central
Publishing Place London
Reviewing status Peer reviewed