HIKESHI silencing can enhance mild hyperthermia sensitivity in human oral squamous cell carcinoma HSC‑3 cells

Tabuchi,Yoshiaki; Maekawa,Keita; Torigoe,Misako; Furusawa,Yukihiro; Hirano,Tetsushi; Minagawa,Satsuki; Yunoki,Tatsuya; Hayashi,Atsushi

doi:10.3892/ijmm.2020.4591

HIKESHI silencing can enhance mild hyperthermia sensitivity in human oral squamous cell carcinoma HSC‑3 cells

Authors:
- Yoshiaki Tabuchi
- Keita Maekawa
- Misako Torigoe
- Yukihiro Furusawa
- Tetsushi Hirano
- Satsuki Minagawa
- Tatsuya Yunoki
- Atsushi Hayashi
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Affiliations: Division of Molecular Genetics Research, Life Science Research Center, University of Toyama, Toyama 930‑0194, Japan, Department of Ophthalmology, Graduate School of Medicine and Pharmaceutical Sciences, University of Toyama, Toyama 930‑0194, Japan, Department of Liberal Arts and Sciences, Toyama Prefectural University, Toyama 939‑0398, Japan
Published online on: April 28, 2020 https://doi.org/10.3892/ijmm.2020.4591
Pages: 58-66
Copyright: © Tabuchi et al. This is an open access article distributed under the terms of Creative Commons Attribution License.

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Abstract

Hyperthermia (HT) is considered to be of value as a treatment modality in various cancers. However, the acquisition of thermotolerance in cancer cells due to the induction of heat shock proteins (HSPs) makes HT less effective. Recent findings have indicated that heat shock protein nuclear import factor hikeshi (HIKESHI), also referred to as C11orf73, acts as a nuclear import carrier of Hsp70 under heat stress conditions. The aim of the present study was to determine whether knockdown (KD) of HIKESHI by small interfering RNA (siRNA) can potentiate mild HT (MHT) sensitivity in human oral squamous cell carcinoma (OSCC) HSC‑3 cells. The mRNA and protein expression of HIKESHI was found to be markedly suppressed in HSC‑3 cells treated with siRNA for HIKESHI (siHIKE). Silencing HIKESHI significantly decreased the cell viability under MHT conditions (42˚C for 90 min). Immunocytochemical and western blot analyses clearly demonstrated that Hsp70 protein translocated from the cytoplasm to the nucleus under MHT conditions, and this translocation was significantly inhibited in cells treated with siHIKE. Treatment of the cells with MHT transiently increased the phosphorylation level of extracellular signal‑regulated kinase (ERK)2. Furthermore, the phosphorylation was sustained in HIKESHI‑KD cells under MHT conditions, and this sustained phosphorylation was abolished by pretreatment with U0126, an inhibitor of mitogen‑activated protein kinase/ERK. In addition, U0126 significantly decreased the viability of cells treated with the combination of HIKESHI‑KD and MHT. The data of the present study suggest that HIKESHI silencing enhanced the sensitivity of human OSCC HSC‑3 cells to MHT.

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