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SOCS‐1 gene delivery cooperates with cisplatin plus pemetrexed to exhibit preclinical antitumor activity against malignant pleural mesothelioma
Author(s) -
Iwahori Kota,
Serada Satoshi,
Fujimoto Minoru,
Ripley Barry,
Nomura Shintaro,
Mizuguchi Hiroyuki,
Shimada Kazuki,
Takahashi Tsuyoshi,
Kawase Ichiro,
Kishimoto Tadamitsu,
Naka Tetsuji
Publication year - 2012
Publication title -
international journal of cancer
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.475
H-Index - 234
eISSN - 1097-0215
pISSN - 0020-7136
DOI - 10.1002/ijc.27611
Subject(s) - pemetrexed , cisplatin , cancer research , apoptosis , in vivo , gene delivery , mesothelioma , stat3 , cell growth , genetic enhancement , biology , pharmacology , medicine , chemotherapy , pathology , gene , biochemistry , genetics , microbiology and biotechnology
Malignant pleural mesothelioma (MPM) is an aggressive tumor with poor prognosis for which an effective therapy remains to be established. This study investigated the therapeutic potential of gene delivery using suppressor of cytokine signaling 1 (SOCS‐1), an endogenous inhibitor of intracellular signaling pathways, for the treatment of MPM. We infected MPM cells (MESO‐4, H28 and H226) with adenovirus‐expressing SOCS‐1 vector to examine the effect of SOCS‐1 overexpression on MPM cells. We evaluated the antitumor effect of SOCS‐1 gene delivery combined with cisplatin plus pemetrexed by cell proliferation, apoptosis and invasion assay. We also investigated the regulation of NF‐κB and STAT3 signaling related to apoptotic pathways. Furthermore, we evaluated the inhibition of tumor growth by SOCS‐1 gene delivery combined with cisplatin plus pemetrexed in vivo . SOCS‐1 gene delivery cooperated with cisplatin plus pemetrexed to inhibit cell proliferation, invasiveness and induction of apoptosis in MPM cells. SOCS‐1 regulated NF‐κB and STAT3 signaling to induce apoptosis in MESO‐4 and H226 cells. Furthermore, SOCS‐1 gene delivery cooperated with cisplatin plus pemetrexed to regulate NF‐κB signaling and significantly inhibit tumor growth of MPM in vivo . These results suggest that SOCS‐1 gene delivery has a potent antitumor effect against MPM and a potential for clinical use in combination with cisplatin plus pemetrexed.