ID 113059
著者
Oda, Asuka Tokushima University
Bat-Erdene, Ariunzaya Tokushima University
Maeda, Yusaku Tokushima University
Takahashi, Mamiko Tokushima University
Iwasa, Masami Tokushima University
キーワード
hyperthermia
plasmacytoma
side population
bortezomib
Pim-2
資料タイプ
学術雑誌論文
抄録
Multiple myeloma (MM) remains incurable, and MM-initiating cells or MM progenitors are considered to contribute to disease relapse through their drug-resistant nature. In order to improve the therapeutic efficacy for MM, we recently developed novel superparamagnetic nanoparticles which selectively accumulate in MM tumors and extirpate them by heat generated with magnetic resonance. We here aimed to clarify the therapeutic effects on MM cells and their progenitors by hyperthermia. Heat treatment at 43°C time-dependently induced MM cell death. The treatment upregulated endoplasmic reticulum (ER) stress mediators, ATF4 and CHOP, while reducing the protein levels of Pim-2, IRF4, c-Myc and Mcl-1. Combination with the proteasome inhibitor bortezomib further enhanced ER stress to potentiate MM cell death. The Pim inhibitor SMI-16a also enhanced the reduction of the Pim-2-driven survival factors, IRF4 and c-Myc, in combination with the heat treatment. The heat treatment almost completely eradicated “side population” fractions in RPMI8226 and KMS-11 cells and suppressed their clonogenic capacity as determined by in vitro colony formation and tumorigenic capacity in SCID mice. These results collectively demonstrated that hyperthermia is able to impair clonogenic drug-resistant fractions of MM cells and enhance their susceptibility to chemotherapeutic drugs.
掲載誌名
Oncotarget
ISSN
19492553
出版者
Impact Journals, LLC
9
12
開始ページ
10307
終了ページ
10316
発行日
2017-12-07
権利情報
Copyright: Miki et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License 3.0 (CC BY 3.0)(https://creativecommons.org/licenses/by/3.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
EDB ID
出版社版DOI
出版社版URL
フルテキストファイル
言語
eng
著者版フラグ
出版社版
部局
病院
医学系
歯学系
薬学系