論文

査読有り
2014年4月

Appropriate Modulation of Autophagy Sensitizes Malignant Peripheral Nerve Sheath Tumor Cells to Treatment With Imatinib Mesylate

JOURNAL OF PEDIATRIC HEMATOLOGY ONCOLOGY
  • Munehiro Okano
  • ,
  • Naoki Sakata
  • ,
  • Satoshi Ueda
  • ,
  • Tsukasa Takemura

36
3
開始ページ
200
終了ページ
211
記述言語
英語
掲載種別
研究論文(学術雑誌)
DOI
10.1097/MPH.0000000000000038
出版者・発行元
LIPPINCOTT WILLIAMS & WILKINS

Malignant peripheral nerve sheath tumor (MPNST), very rare in childhood, is a highly aggressive soft-tissue tumor. We experienced a case of a 7-year-old boy with MPNST who was treated with imatinib mesylate (imatinib) after the identification of platelet-derived growth factor receptor expression in his tumor. We were unable to observe clinical benefits of imatinib in this patient. Therefore, cellular reactions of imatinib were investigated in vitro using 3 MPNST cell lines. Imatinib induced cytotoxicity in vitro with variable IC50 values (11.7 to >30 M). Induction of apoptosis was not a pivotal mechanism in the inhibitory effects. We found that the treatment of MPNST cell lines with imatinib induced autophagy. Suppression of the initiation of autophagy by 3-methyladenine or small interfering RNA (siRNA) against beclin-1 attenuated the imatinib-mediated cytotoxicity. In contrast, blocking the formation of autophagosomes or the development of autolysosomes using siRNA against microtubule-associated protein light chain 3B, bafilomycin A1, chloroquine, or an MEK1/2 inhibitor (U0126) enhanced the imatinib-induced cytotoxicity in MPNST cells. Our data showed that the imatinib-mediated autophagy can function as a cytotoxic mechanism and that appropriate modulation of autophagy may sensitize MPNST cells to imatinib, which in turn may be a novel therapeutic strategy for MPNST.

Web of Science ® 被引用回数 : 1

リンク情報
DOI
https://doi.org/10.1097/MPH.0000000000000038
PubMed
https://www.ncbi.nlm.nih.gov/pubmed/24136016
Web of Science
https://gateway.webofknowledge.com/gateway/Gateway.cgi?GWVersion=2&SrcAuth=JSTA_CEL&SrcApp=J_Gate_JST&DestLinkType=FullRecord&KeyUT=WOS:000335352400023&DestApp=WOS_CPL
ID情報
  • DOI : 10.1097/MPH.0000000000000038
  • ISSN : 1077-4114
  • eISSN : 1536-3678
  • PubMed ID : 24136016
  • Web of Science ID : WOS:000335352400023

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