2-Deoxy-glucose Enhances the Effect of Cisplatin and Pemetrexed in Reducing Malignant Pleural Mesothelioma Cell Proliferation But Not Spheroid Growth

Our plain-English summary of 2-Deoxy-glucose Enhances the Effect of Cisplatin and Pemetrexed in Reducing Malignant Pleural Mesothelioma Cell Proliferation But Not Spheroid Growth, by I. Gerogianni, E. Pitaraki, R.M. Jagirdar, et al (Anticancer Research, 2019).

The study

• Authors: I. Gerogianni, E. Pitaraki, R.M. Jagirdar, O. Kouliou, L. Giannakou, S. Giannopoulos, E. Papazoglou, C. Hatzoglou, K.I. Gourgoulianis, S.G. Zarogiannis
• Journal: Anticancer Research
• Published: 2019;39(7):3809-3814
• Cited by: 12 articles, as counted by NIH iCite
• Read it: PubMed · Publisher

Abstract

Background/aim: Malignant pleural mesothelioma (MPM) is a therapy-resistant neoplasm of the pleura. Standard chemotherapy consists of a combination of cisplatin (CPDD) and pemetrexed (PEM). The aim of this study was to assess whether inhibition of aerobic glycolysis by 2-deoxy-glucose (2DG) would enhance the effects of standard chemotherapy.

Materials And Methods: MeT-5A, M14K, MSTO and ZL34 cell lines were used. Cell viability with 2DG and cell proliferation and spheroid formation with CPDD+PEM alone and with 2-DG were tested.

Results: Viability with 2-DG was dose-dependent. Cell proliferation with CPDD+PEM on 2D surface was reduced in all cell types, 2-DG inclusion demonstrated a synergistic effect in MSTO and ZL34 cells. Spheroid growth in 3D with CPDD+PEM or CPDD+PEM+2-DG lowered spheroid growth in all cell types.

Conclusion: 2-DG synergizes with CPDD+PEM in lowering MPM cell proliferation in 2D to <20%. In 3D MPM spheroid growth 2-DG synergism with CPDD+PEM treatment is not maintained.

Copyright© 2019, International Institute of Anticancer Research (Dr. George J. Delinasios), All rights reserved.

In plain English

This was a laboratory study of cells grown in dishes. It did not study people or asbestos exposure. The authors tested whether adding 2-deoxy-glucose (2-DG), a substance that blocks how cells use sugar for energy, to the standard mesothelioma chemotherapy drugs cisplatin and pemetrexed would increase the drugs' effect. They used one benign (non-cancerous) mesothelial cell line and three malignant pleural mesothelioma cell lines: epithelioid, biphasic and sarcomatoid. 2-DG alone reduced cell viability in all cell types as the dose increased. On flat (2D) surfaces, the two drugs reduced cell growth in all cell types. Adding 2-DG gave a statistically significant further reduction in the biphasic line (from 16.0% to 5.4% of control) and the sarcomatoid line (from 29.6% to 12.5%). In three-dimensional cell clusters called spheroids, both treatments reduced the mean spheroid perimeter to between 67.0% and 78.3% of control. The authors described the spheroids as equally sensitive to both treatments. The authors concluded that 2-DG enhanced the drugs' reduction of 2D cell growth, and that further experiments are required.

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 experiment, with flat 2D cultures and 3D spheroid cultures
• Who was studied: Four cell lines: MeT-5A (benign mesothelial cells), M14K (epithelioid malignant pleural mesothelioma), MSTO-211H (biphasic) and ZL34 (sarcomatoid). No human subjects. Dates are not given.
• Exposure: No asbestos exposure was studied. The exposures were drugs: 2-deoxy-glucose (2-DG, 0.5 to 3.0 mM in the viability tests), and cisplatin (10 μM) plus pemetrexed (200 μM), given with or without 2-DG (3.0 mM).
• Main results:
  • 2-DG alone significantly reduced viability in all four cell types as the dose increased from 0.5 mM to 3.0 mM.
  • Benign MeT-5A cells on 2D surfaces: cell proliferation was 23.0±4.0% of control with cisplatin plus pemetrexed, and 10.6±0.6% with 2-DG added (both significantly lower than control).
  • Epithelioid M14K cells on 2D surfaces: cell proliferation was 13.0±0.8% with cisplatin plus pemetrexed, and 11.2±0.5 with 2-DG added (both significantly lower than control).
  • Biphasic MSTO cells on 2D surfaces: cell proliferation was 16.0±0.7% with cisplatin plus pemetrexed, and 5.4±0.1% with 2-DG added (control 98.7±2.5%).
  • In biphasic MSTO cells, proliferation with 2-DG plus cisplatin and pemetrexed was significantly lower than with cisplatin and pemetrexed alone.
  • Sarcomatoid ZL34 cells on 2D surfaces: cell proliferation was 29.6±1.0% with cisplatin plus pemetrexed, and 12.5±0.7 with 2-DG added (both significantly lower than control).
  • In sarcomatoid ZL34 cells, proliferation with 2-DG plus cisplatin and pemetrexed was significantly lower than with cisplatin and pemetrexed alone.
  • In 3D spheroids, the authors reported that all cell types were equally sensitive to cisplatin plus pemetrexed with and without 2-DG.
  • MeT-5A spheroids: mean perimeter was 68.9±1.4% of control with cisplatin plus pemetrexed, and 69.5±2.3% with 2-DG added.
  • M14K spheroids: mean perimeter was 67.0±1.6% with cisplatin plus pemetrexed, and 69.6±2.3% with 2-DG added.
  • MSTO spheroids: mean perimeter was 78.3±1.7% with cisplatin plus pemetrexed, and 77.0±1.8% with 2-DG added.
  • ZL34 spheroids: mean perimeter was 74.9±1.7% with cisplatin plus pemetrexed, and 72.5±1.1% with 2-DG added.
• The authors' conclusion: The authors concluded that cisplatin and pemetrexed combined with 2-DG enhanced the reduction of 2D cell proliferation, which they described as relevant to tumor growth and spread in the thoracic wall and lung tissue. Separately, they stated that in spheroids, adding 2-DG did not further decrease growth.
• Limitations the authors state:
  • The authors stated that further experiments are required to determine the potential of 2-DG against mesothelioma tumor growth and progression.

Topics

The National Library of Medicine indexes this study under subjects our site covers: Lung cancer, Mesothelioma.

Medical terms in this study, explained in our Lexicon: Cisplatin, Pemetrexed (Alimta), Pleural Mesothelioma, Neoplasm, Pleura, Chemotherapy, Synergistic Effect.

Related studies

• Interaction and cross-resistance of cisplatin and pemetrexed in malignant pleural mesothelioma cell lines — M. Kitazono-Saitoh, Y. Takiguchi, et al. (2012)
• Combined hyaluronate-based films loaded with pemetrexed and cisplatin for the treatment of malignant pleural mesothelioma: Preliminary evaluation in an orthotopic tumor recurrence model — F. Sonvico, S. Barbieri, et al. (2018)
• Overexpression of Numb suppresses tumor cell growth and enhances sensitivity to cisplatin in epithelioid malignant pleural mesothelioma — Y. Kang, M. Ding, et al. (2013)
• Vorinostat eliminates multicellular resistance of mesothelioma 3D spheroids via restoration of Noxa expression — D. Barbone, P. Cheung, et al. (2012)
• Nintedanib in combination with pemetrexed and cisplatin for chemotherapy-naive patients with advanced malignant pleural mesothelioma (LUME-Meso): a double-blind, randomised, placebo-controlled phase 3 trial — G.V. Scagliotti, R. Gaafar, et al. (2019)
• A phase Ib study of GSK3052230, an FGF ligand trap in combination with pemetrexed and cisplatin in patients with malignant pleural mesothelioma — E.M.J. van Brummelen, E. Levchenko, et al. (2020)

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