Open AccessSynergistic effect of non‐transmissible Sendai virus vector encoding the c‐myc suppressor FUSE‐binding protein‐interacting repressor plus cisplatin in the treatment of malignant pleural mesothelioma
Author(s) -
Kitamura Atsushi,
Matsushita Kazuyuki,
Takiguchi Yuichi,
Shimada Hideaki,
Tada Yuji,
Yamanaka Makako,
Hiroshima Kenzo,
Tagawa Masatoshi,
Tomonaga Takeshi,
Matsubara Hisahiro,
Inoue Makoto,
Hasegawa Mamoru,
Sato Yasunori,
Levens David,
Tatsumi Koichiro,
Nomura Fumio
Publication year - 2011
Publication title -
cancer science
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.035
H-Index - 141
eISSN - 1349-7006
pISSN - 1347-9032
DOI - 10.1111/j.1349-7006.2011.01931.x
Subject(s) - repressor , suppressor , sendai virus , cisplatin , virology , cancer research , mesothelioma , biology , medicine , virus , pathology , chemotherapy , gene , cancer , genetics , transcription factor
Human malignant pleural mesothelioma (HMPM) is highly resistant to conventional therapy, and therefore novel therapies are required. We previously reported that overexpression of the FUSE‐binding protein‐interacting repressor (FIR), a c‐myc transcriptional repressor, induces apoptosis via c‐Myc suppression, and is thus a suitable cancer therapy. In the current preclinical trial, a fusion gene deleted non‐transmissible Sendai virus vector encoding FIR (SeV/ΔF/FIR) was prepared and its cytotoxic activity against an orthotopic xenograft model of HMPM, in combination with cisplatin, was assessed. SeV/ΔF/FIR and a fusion gene deleted non‐transmissible Sendai virus vector encoding green fluorescent protein (SeV/ΔF/GFP) were prepared. The transduction efficiency of these agents in terms of dose‐dependent cytotoxicity and/or apoptosis induction was then assessed in a few HMPM cells. Combination therapy with SeV/ΔF/FIR plus cisplatin was evaluated in vitro and in a mouse model. SeV/ΔF/FIR significantly reduced cell viability in three HMPM cell lines but was less effective in non‐tumor immortalized mesothelial cells. SeV/ΔF/FIR cytotoxicity was partly due to apoptosis induction via c‐Myc suppression. In addition, SeV/ΔF/FIR showed synergistic antitumor effects in combination with cisplatin, as was revealed by isobologram analysis in MSTO‐211H. Moreover, combination therapy with SeV/ΔF/FIR plus cisplatin demonstrated significant tumor reduction and improvement in survival rate in an animal model. Combination therapy with SeV/ΔF/FIR plus cisplatin has therapeutic potential against HMPM. SeV/ΔF/FIR plus cisplatin will be an attractive modality against HMPM in the future. ( Cancer Sci 2011; 102: 1366–1373)