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

TitleInterferon-β produces synergistic combinatory anti-tumor effects with cisplatin or pemetrexed on mesothelioma cells.
Publication TypeJournal Article
Year of Publication2013
AuthorsLi Q, Kawamura K, Yang S, Okamoto S, Kobayashi H, Tada Y, Sekine I, Takiguchi Y, Shingyouji M, Tatsumi K, Shimada H, Hiroshima K, Tagawa M
JournalPloS one
Volume8
Issue8
Paginatione72709
Date Published2013
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.

DOI10.1158/0008-5472.CAN-13-1000
Alternate JournalPLoS ONE