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Open AccessArticle

In Vitro Characterization of Cisplatin and Pemetrexed Effects in Malignant Pleural Mesothelioma 3D Culture Phenotypes

1
Department of Physiology, Faculty of Medicine, University of Thessaly, Biopolis, 41500 Larissa, Greece
2
Department of Respiratory Medicine, Faculty of Medicine, University of Thessaly, Biopolis, 41500 Larissa, Greece
*
Author to whom correspondence should be addressed.
Cancers 2019, 11(10), 1446; https://doi.org/10.3390/cancers11101446
Received: 18 August 2019 / Revised: 20 September 2019 / Accepted: 25 September 2019 / Published: 27 September 2019
(This article belongs to the Special Issue Cancer Organoids in Basic Science and Translational Medicine)
Malignant pleural mesothelioma (MPM) is an aggressive cancer with poor prognosis. The main treatment for MPM is doublet chemotherapy with Cisplatin and Pemetrexed, while ongoing trials test the efficacy of pemetrexed monotherapy. However, there is lack of evidence regarding the effects of Cisplatin and Pemetrexed on MPM cell phenotypes, especially in three-dimensional (3D) cell cultures. In this study, we evaluated the effects Cisplatin and Pemetrexed on cell viability using homologous cell derived extracellular matrix (hECM) as substratum and subsequently in the following 3D cell culture phenotypes: tumor spheroid formation, tumor spheroid invasion, and collagen gel contraction. We used benign mesothelial MeT-5A cells as controls and the MPM cell lines M14K (epithelioid), MSTO (biphasic), and ZL34 (sarcomatoid). Cell viability of all cell lines was significantly decreased with all treatments. Mean tumor spheroid perimeter was reduced after treatment with Pemetrexed or the doublet therapy in all cell lines, while Cisplatin reduced the mean spheroid perimeter of MeT-5A and MSTO cells. Doublet treatment reduced the invasive capacity of spheroids of cell lines into collagenous matrices, while Cisplatin lowered the invasion of the MSTO and ZL34 cell lines, and Pemetrexed lowered the invasion of MeT-5A and ZL34 cell lines. Treatment with Pemetrexed or the combination significantly reduced the collagen gel contraction of all cell lines, while Cisplatin treatment affected only the MeT-5A and M14K cells. The results of the current study can be used as an in vitro 3D platform for testing novel drugs against MPM for ameliorating the effects of first line chemotherapeutics. View Full-Text
Keywords: 3D cultures; cisplatin; homologous cell derived extracellular matrix; malignant pleural mesothelioma; mesothelial cells; pemetrexed; pleura; tumor spheroid 3D cultures; cisplatin; homologous cell derived extracellular matrix; malignant pleural mesothelioma; mesothelial cells; pemetrexed; pleura; tumor spheroid
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MDPI and ACS Style

Papazoglou, E.D.; Jagirdar, R.M.; Kouliou, O.A.; Pitaraki, E.; Hatzoglou, C.; Gourgoulianis, K.I.; Zarogiannis, S.G. In Vitro Characterization of Cisplatin and Pemetrexed Effects in Malignant Pleural Mesothelioma 3D Culture Phenotypes. Cancers 2019, 11, 1446. https://doi.org/10.3390/cancers11101446

AMA Style

Papazoglou ED, Jagirdar RM, Kouliou OA, Pitaraki E, Hatzoglou C, Gourgoulianis KI, Zarogiannis SG. In Vitro Characterization of Cisplatin and Pemetrexed Effects in Malignant Pleural Mesothelioma 3D Culture Phenotypes. Cancers. 2019; 11(10):1446. https://doi.org/10.3390/cancers11101446

Chicago/Turabian Style

Papazoglou, Eleftherios D.; Jagirdar, Rajesh M.; Kouliou, Olympia A.; Pitaraki, Eleanna; Hatzoglou, Chrissi; Gourgoulianis, Konstantinos I.; Zarogiannis, Sotirios G. 2019. "In Vitro Characterization of Cisplatin and Pemetrexed Effects in Malignant Pleural Mesothelioma 3D Culture Phenotypes" Cancers 11, no. 10: 1446. https://doi.org/10.3390/cancers11101446

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