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Suppressor of cytokine signaling-1 expression by infectivity-enhanced adenoviral vector inhibits IL-6-dependent proliferation of multiple myeloma cells.

Abstract：

:Multiple myeloma (MM) accounts for 10% of hematological malignant disorders. Its refractory nature indicates the necessity of developing novel therapeutic modalities. Since interleukin 6 (IL-6) is one of the major growth factors for MM cells, we expressed suppressor of cytokine signaling-1 (SOCS-1), one of the blockades of IL-6 receptor downstream signaling, to suppress the proliferation of MM cells. Because MM cells are resistant to conventional adenoviral vector infection, we utilized infectivity-enhanced adenoviral vectors with an RGD4C motif in the adenoviral fiber-knob region (RGD-modified vector). In infectivity analysis, RGD-modified vectors were superior to unmodified controls in the majority of the MM cell lines tested. The overexpression of SOCS-1 using infectivity-enhanced adenoviral vectors achieved growth suppression in IL-6-dependent MM cells, but not in the IL-6-independent cells. IL-6-induced STAT3 phosphorylation was suppressed in IL-6-dependent cells, indicating that the signal transduction cascade of the IL-6 receptor signaling was blocked. In aggregate, SOCS-1 overexpression with RGD-modified adenoviral vectors achieved the antiproliferative effect in IL-6-dependent MM cells. These results provide an initial proof-of-principle of the anticancer effect of SOCS-1 expression vector as well as a promise for the future development of therapeutic modality for MM based on this vector.

journal_name

Cancer Gene Ther

journal_title

Cancer gene therapy

authors

Yamamoto M,Nishimoto N,Davydova J,Kishimoto T,Curiel DT

doi

10.1038/sj.cgt.7700873

subject

Has Abstract

pub_date

2006-02-01 00:00:00

pages

194-202

issue

2

eissn

0929-1903

issn

1476-5500

pii

7700873

journal_volume

13

pub_type

杂志文章

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