ID 113059
Author
Oda, Asuka Tokushima University
Bat-Erdene, Ariunzaya Tokushima University
Maeda, Yusaku Tokushima University
Takahashi, Mamiko Tokushima University
Iwasa, Masami Tokushima University
Keywords
hyperthermia
plasmacytoma
side population
bortezomib
Pim-2
Content Type
Journal Article
Description
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.
Journal Title
Oncotarget
ISSN
19492553
Publisher
Impact Journals, LLC
Volume
9
Issue
12
Start Page
10307
End Page
10316
Published Date
2017-12-07
Rights
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
DOI (Published Version)
URL ( Publisher's Version )
FullText File
language
eng
TextVersion
Publisher
departments
University Hospital
Medical Sciences
Oral Sciences
Pharmaceutical Sciences