Open AccessMolecular mechanism underlying the antiproliferative effect of suppressor of cytokine signaling‐1 in non‐small‐cell lung cancer cells
Author(s) -
Shimada Kazuki,
Serada Satoshi,
Fujimoto Minoru,
Nomura Shintaro,
Nakatsuka Rie,
Harada Emi,
Iwahori Kota,
Tachibana Isao,
Takahashi Tsuyoshi,
Kumanogoh Atsushi,
Kishimoto Tadamitsu,
Naka Tetsuji
Publication year - 2013
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/cas.12266
Subject(s) - cancer research , epidermal growth factor receptor , signal transduction , a549 cell , cell growth , biology , lung cancer , cytokine , focal adhesion , janus kinase , epidermal growth factor , cell , cancer , microbiology and biotechnology , immunology , receptor , medicine , biochemistry , genetics
Lung cancer ( LC ) is the major cause of death by cancer and the number of LC patients is increasing worldwide. 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 LC . To examine the antitumor effect of SOCS ‐1 overexpression on non‐small‐cell lung cancer ( NSCLC ) cells, NSCLC cells ( A 549, LU 65, and PC 9) were infected with adenovirus‐expressing SOCS ‐1 vector. The cell proliferation assay showed that A 549 and LU 65, but not PC 9, were sensitive to SOCS ‐1 gene‐mediated suppression of cell growth. Although JAK inhibitor I could also inhibit proliferation of A 549 and LU 65 cells, SOCS ‐1 gene delivery appeared to be more potent as SOCS ‐1 could suppress focal adhesion kinase and epidermal growth factor receptor, as well as the JAK / STAT 3 signaling pathway. Enhanced phosphorylation of the p53 protein was detected by means of phospho‐kinase array in SOCS ‐1 overexpressed A 549 cells compared with control cells, whereas no phosphorylation of p53 was observed when JAK inhibitor I was used. Furthermore, treatment with adenoviral vector Ad SOCS ‐1 in vivo significantly suppressed NSCLC proliferation in a xenograft model. These results suggest that the overexpression of SOCS ‐1 gene is effective for antitumor therapy by suppressing the JAK / STAT , focal adhesion kinase, and epidermal growth factor receptor signaling pathways and enhancing p53‐mediated antitumor activity in NSCLC .