Interferon-β produces synergistic combinatory anti-tumor effects with cisplatin or pemetrexed on mesothelioma cells

Our plain-English summary of Interferon-β produces synergistic combinatory anti-tumor effects with cisplatin or pemetrexed on mesothelioma cells, by Q. Li, K. Kawamura, S. Yang, et al (PloS One, 2013).

The study

• Authors: Q. Li, K. Kawamura, S. Yang, S. Okamoto, H. Kobayashi, Y. Tada, I. Sekine, Y. Takiguchi, M. Shingyouji, K. Tatsumi, H. Shimada, K. Hiroshima, M. Tagawa
• Journal: PloS One
• Published: 2013;8(8):e72709
• Cited by: 11 articles, as counted by NIH iCite
• Read it: PubMed · Publisher · Free full text

Abstract

Interferons (IFNs) have been tested for the therapeutic effects in various types of malignancy, but mechanisms of the anti-tumors effects and the differential biological activities among IFN members are dependent on respective cell types. In this study, we examined growth inhibitory activities of type I and III IFNs on 5 kinds of human mesothelioma cells bearing wild-type p53 gene, and showed that type I IFNs but not type III IFNs decreased the cell viabilities. Moreover, growth inhibitory activities and up-regulated expression levels of the major histocompatibility complexes class I antigens were greater with IFN-β than with IFN-α treatments. Cell cycle analyses demonstrated that type I IFNs increased S- and G2/M-phase populations, and subsequently sub-G1-phase fractions. The cell cycle changes were also greater with IFN-β than IFN-α treatments, and these data collectively showed that IFN-β had stronger biological activities than IFN-α in mesothelioma. Type I IFNs-treated cells increased p53 expression and the phosphorylation levels, and activated apoptotic pathways. A combinatory use of IFN-β and cisplatin or pemetrexed, both of which are the current first-line chemotherapeutic agents for mesothelioma, produced synergistic anti-tumor effects, which were also evidenced by increased sub-G1-phase fractions. These data demonstrated firstly to our knowledge that IFN-β produced synergistic anti-tumor effects with cisplatin or pemetrexed on mesothelioma through up-regulated p53 expression.

In plain English

This was a laboratory study of cells grown in culture. No patients or animals were studied, and asbestos exposure was not examined. The authors tested interferons, which are immune signalling proteins, on five human mesothelioma cell lines carrying the normal (wild-type) p53 gene. They also tested Met-5A cells, an immortalized line derived from mesothelium. Two type I interferons, IFN-α and IFN-β, reduced mesothelioma cell growth, and IFN-β had the stronger effect. A type III interferon, IFN-λ1, did not reduce growth, and the mesothelioma cells did not express one of its receptor genes, IL-28Rα. In two cell lines, IFN-β raised levels of the p53 protein and its activated form. When IFN-β was combined with cisplatin or pemetrexed, the current first-line drugs for mesothelioma, the combined effects were synergistic in most cell lines, with some exceptions at higher effect levels. The authors concluded that IFN-β had greater biological activity than IFN-α in mesothelioma cells, activated p53 pathways, and enhanced the anti-tumor effects of the first-line drugs.

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
• Who was studied: Five human mesothelioma cell lines (NCI-H2452, NCI-H2052, NCI-H226, NCI-H28 and MSTO-211H), plus mesothelium-derived Met-5A cells immortalized with SV40 T antigen; human esophageal carcinoma T.Tn cells were used as a positive control for IFN-λ1
• Exposure: No asbestos exposure was studied. Cells were treated with IFN-α2a, IFN-β1a or IFN-λ1 at different doses, and with cisplatin (CDDP) or pemetrexed (PEM) combined with IFNs
• Main results:
  • Type I IFNs (IFN-α and IFN-β), but not type III IFN, suppressed proliferation of the mesothelioma cells; IFN-β was more inhibitory than IFN-α
  • In RT-PCR analyses, all the mesothelioma cell lines expressed only one of the two type III IFN receptor genes (IL-10Rβ) and did not express IL-28Rα
  • Type I IFN-treated cells showed increased S- and G2/M-phase populations, followed by increased sub-G1 (dying cell) fractions; Met-5A cells did not show increased sub-G1 populations
  • In NCI-H2052 and NCI-H28 cells, IFN-β raised p53 levels and p53 phosphorylation; these changes were undetectable or minimal with IFN-α
  • IFN-β plus cisplatin was synergistic in most cell lines, except NCI-H2452 above 0.3 Fa points and NCI-H28 above 0.4 Fa points
  • IFN-β plus pemetrexed was synergistic in all cell lines at Fa points between 0.3 and 0.7, except NCI-H226 above 0.6 Fa points
  • In NCI-H2052 and NCI-H28 cells, sub-G1 fractions were greater with IFN-β combined with cisplatin or pemetrexed than with either treatment alone
• The authors' conclusion: The authors concluded that IFN-β had greater biological activity than IFN-α in mesothelioma, activated p53 pathways and enhanced the anti-tumor effects of the first-line chemotherapy drugs
• Limitations the authors state:
  • The authors stated that further investigation is needed to understand why the extrinsic apoptotic pathway was preferentially activated in mesothelioma cells

Topics

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

Medical terms in this study, explained in our Lexicon: Cisplatin, Pemetrexed (Alimta), Mesothelioma.

Related studies

• Zoledronic acid produces combinatory anti-tumor effects with cisplatin on mesothelioma by increasing p53 expression levels — S. Okamoto, Y. Jiang, et al. (2013)
• Upregulated p53 expression activates apoptotic pathways in wild-type p53-bearing mesothelioma and enhances cytotoxicity of cisplatin and pemetrexed — Q. Li, K. Kawamura, et al. (2012)
• Interaction and cross-resistance of cisplatin and pemetrexed in malignant pleural mesothelioma cell lines — M. Kitazono-Saitoh, Y. Takiguchi, et al. (2012)
• COX-2 specific inhibitors enhance the cytotoxic effects of pemetrexed in mesothelioma cell lines — S.L. O'Kane, G.L. Eagle, et al. (2010)
• Preclinical emergence of vandetanib as a potent antitumour agent in mesothelioma: molecular mechanisms underlying its synergistic interaction with pemetrexed and carboplatin — E. Giovannetti, P.A. Zucali, et al. (2011)
• Putative cancer stem cells in malignant pleural mesothelioma show resistance to cisplatin and pemetrexed — L. Cortes-Dericks, G.L. Carboni, et al. (2010)

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