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

Our plain-English summary of In Vitro Characterization of Cisplatin and Pemetrexed Effects in Malignant Pleural Mesothelioma 3D Culture Phenotypes, by E.D. Papazoglou, R.M. Jagirdar, O.A. Kouliou, et al (Cancers, 2019).

The study

• Authors: E.D. Papazoglou, R.M. Jagirdar, O.A. Kouliou, E. Pitaraki, C. Hatzoglou, K.I. Gourgoulianis, S.G. Zarogiannis
• Journal: Cancers
• Published: 2019;11(10)
• Cited by: 17 articles, as counted by NIH iCite
• Read it: PubMed · Publisher · Free full text

Abstract

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.

In plain English

This laboratory study tested two chemotherapy drugs for malignant pleural mesothelioma, cisplatin and pemetrexed, alone and together, on human cell lines. It did not study asbestos exposure or patients. Benign mesothelial cells (MeT-5A) served as controls, alongside three mesothelioma cell lines: M14K (epithelioid), MSTO (biphasic) and ZL34 (sarcomatoid). The authors measured cell survival on a matrix made by the same type of cells. They also ran three three-dimensional tests: growth of cell clusters (spheroids), spheroid invasion into collagen, and contraction of collagen gels. All treatments lowered cell survival in all four cell lines. In M14K cells, for example, survival was 63.83% with cisplatin and 21.84% with pemetrexed, compared with untreated cells. Pemetrexed reduced spheroid size and gel contraction in all cell lines. In the three-dimensional tests, cisplatin alone reduced spheroid size in MeT-5A and MSTO cells, invasion in MSTO and ZL34 cells, and gel contraction in MeT-5A and M14K cells. The combination reduced spheroid invasion in all lines. The authors reported that in most cases it was not better than pemetrexed alone. The authors concluded that this three-dimensional platform can be used to assess additional (adjuvant) drugs for mesothelioma treatment.

We wrote this plain-English summary from the full article with the help of AI, and a second AI model checked each sentence against the article. It is not the authors' wording; the abstract and the article are their own account.

What the study did and found

• Design: laboratory (in vitro) cell culture study, including three-dimensional culture assays
• Who was studied: four human cell lines: MeT-5A (benign immortalized mesothelial cells, used as controls), M14K (epithelioid MPM), MSTO (biphasic MPM) and ZL34 (sarcomatoid MPM). No patients or animals were studied as subjects.
• Exposure: chemotherapy drugs, not asbestos: cisplatin (CPDD) at 10 to the minus 5 M (10 µM), pemetrexed (Pem) at 2 × 10 to the minus 4 M, and the two drugs combined
• Main results:
  • Cisplatin, pemetrexed and the combination each reduced cell survival in all four cell lines. Pemetrexed or the combination was more potent than cisplatin alone in the mesothelioma cell lines.
  • In M14K cells, survival as a percentage of untreated controls was 63.83% with cisplatin, 21.84% with pemetrexed and 21.02% with the combination
  • All treatments reduced spheroid size in MeT-5A and MSTO cells. M14K and ZL34 spheroids were smaller only with pemetrexed or the combination.
  • Cisplatin reduced spheroid invasion into collagen in MSTO and ZL34 cells, and pemetrexed did so in MeT-5A and ZL34 cells. The combination significantly reduced invasion in all cell lines.
  • Pemetrexed reduced collagen gel contraction in all cell lines. Cisplatin did so only in MeT-5A and M14K cells.
  • In the three-dimensional tests, the combination was in most cases not better than pemetrexed alone
• The authors' conclusion: The authors concluded that a three-dimensional cell culture platform can be used to assess the efficacy of adjuvant drugs for mesothelioma treatment

Topics

Medical terms in this study, explained in our Lexicon: Cisplatin, Pemetrexed (Alimta), Pleural Mesothelioma, Prognosis, Chemotherapy, Collagen, MeT-5A Cells, Epithelioid.

Related studies

• 2-Deoxy-glucose Enhances the Effect of Cisplatin and Pemetrexed in Reducing Malignant Pleural Mesothelioma Cell Proliferation But Not Spheroid Growth — I. Gerogianni, E. Pitaraki, et al. (2019)
• Cell and extracellular matrix interaction models in benign mesothelial and malignant pleural mesothelioma cells in 2D and 3D in-vitro — R.M. Jagirdar, E.D. Papazoglou, et al. (2021)
• Liposomal pemetrexed: formulation, characterization and in vitro cytotoxicity studies for effective management of malignant pleural mesothelioma — N. Essam Eldin, H.M. Elnahas, et al. (2015)
• Matrigel-based organoid culture of malignant mesothelioma reproduces cisplatin sensitivity through CTR1 — F. Ito, K. Kato, et al. (2023)
• Folic acid phenotype (FAP) is a superior biomarker predicting response to pemetrexed-based chemotherapy in malignant pleural mesothelioma — F.D. Mairinger, C. Vollbrecht, et al. (2017)
• Adaptation of a chemosensitivity assay to accurately assess pemetrexed in ex vivo cultures of lung cancer — S.L. Suchy, R.J. Landreneau, et al. (2013)

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