ダウンロード数 : ?
ファイル
言語
英語
著者
稲尾 瞳子
原嶋 奈々江
門馬 浩行
Okano, Shinji
板倉 正幸
田中 恒夫
内容記述(抄録等)
Innate adjuvant receptors are expressed in immune cells and some types of cancers. If antitumor therapies targeting these receptors are established, it is likely that they will be therapeutically beneficial because antitumor effects and immune-cell activation can be induced simultaneously. In this study, we tested this possibility of using an innate adjuvant receptor ligand, polyinosinic-polycytidylic acid [poly(I:C)], to treat human breast cancer cell lines. Three breast cancer cell lines (MCF-7, MDA-MB-231, and BT-549) were used in this study. Poly(I:C) was transfected into these cancer cells to stimulate melanoma differentiation-associated gene (MDA) 5, which is a cytoplasmic adjuvant receptor. Poly(I:C) transfection significantly reduced the viability of all cell lines in a manner partially dependent on MDA5. Flow cytometeric analyses and immunoblot assays revealed that the antitumor effect depended on both caspase-dependent apoptosis and c-Myc- and cyclinD1-dependent growth arrest. Interestingly, poly(I:C) transfection was accompanied by autophagy, which is thought to protect cancer cells from apoptosis after poly(I:C) transfection. In a xenograft mouse model, local transfection of poly(I:C) significantly inhibited the growth of xenografted MDA-MB-231 cells. Our findings indicate that cytoplasmic delivery of poly(I:C) can induce apoptosis and growth arrest of human breast cancer cells, and that therapy-associated autophagy prevents apoptosis. The results of this study suggest that the innate adjuvant receptors are promising targets and that their ligands could serve as antitumor reagents, which have the potential to simultaneously induce antitumor effects and activate immune cells.
主題
Apoptosis
Growth arrest
Poly(I:C)
MDA5
Autophagy
掲載誌名
Breast cancer research and treatment
134
1
開始ページ
89
終了ページ
100
ISSN
01676806
発行日
2012-07
DOI
DOI公開日
2017-03-15
PubMed ID
NCID
AA10623184
出版者
Springer
資料タイプ
学術雑誌論文
ファイル形式
PDF
権利関係
© Springer Science+Business Media, LLC. 2011
著者版/出版社版
著者版
業績ID
e16180
e30938
e14861
e17198
部局
医学部
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