title: Interferon-β produces synergistic combinatory anti-tumor effects with cisplatin or pemetrexed on mesothelioma cells.
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.
authors: Division of Pathology and Cell Therapy, Chiba Cancer Center Research Institute, Chiba, Japan.
authors: Quanhai
authors: Q
authors: Li
authors: Kiyoko
authors: K
authors: Kawamura
authors: Shan
authors: S
authors: Yang
authors: Shinya
authors: S
authors: Okamoto
authors: Hiroshi
authors: H
authors: Kobayashi
authors: Yuji
authors: Y
authors: Tada
authors: Ikuo
authors: I
authors: Sekine
authors: Yuichi
authors: Y
authors: Takiguchi
authors: Masato
authors: M
authors: Shingyouji
authors: Koichiro
authors: K
authors: Tatsumi
authors: Hideaki
authors: H
authors: Shimada
authors: Kenzo
authors: K
authors: Hiroshima
authors: Masatoshi
authors: M
authors: Tagawa
mesh_terms: D000970:Antineoplastic Agents / Q000494:pharmacology / Q000627:therapeutic use; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000494:pharmacology / Q000627:therapeutic use*; D017209:Apoptosis / Q000187:drug effects; D002453:Cell Cycle / Q000187:drug effects; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D002945:Cisplatin / Q000494:pharmacology / Q000627:therapeutic use*; D004357:Drug Synergism; D005971:Glutamates / Q000494:pharmacology / Q000627:therapeutic use*; D006147:Guanine / Q000031:analogs & derivatives* / Q000494:pharmacology / Q000627:therapeutic use; D006801:Humans; D016899:Interferon-beta / Q000494:pharmacology / Q000627:therapeutic use*; D008654:Mesothelioma / Q000188:drug therapy* / Q000473:pathology; D000068437:Pemetrexed; D017471:Receptors, Interferon / Q000378:metabolism; D015398:Signal Transduction / Q000187:drug effects; D016159:Tumor Suppressor Protein p53 / Q000378:metabolism
chemical_list: D000970:Antineoplastic Agents; D005971:Glutamates; D017471:Receptors, Interferon; D016159:Tumor Suppressor Protein p53; D000068437:Pemetrexed; D006147:Guanine; D016899:Interferon-beta; D002945:Cisplatin
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