Role of HIKESHI on Hyperthermia for Castration-Resistant Prostate Cancer and Application of a Novel Magnetic Nanoparticle with Carbon Nanohorn for Magnetic Hyperthermia

Author:

Nagai Takashi1,Kawai Noriyasu1ORCID,Gonda Masakazu1,Iida Keitaro1,Etani Toshiki1ORCID,Kobayashi Daichi1,Naiki Taku1ORCID,Naiki-Ito Aya2ORCID,Ando Ryosuke1,Yamaguchi Sataro3,Sugahara Yuto4,Ueno Sakyo4,Tsutsumiuchi Kaname4,Imae Toyoko5,Yasui Takahiro1ORCID

Affiliation:

1. Department of Nephron-Urology, Graduate School of Medical Sciences, Nagoya City University, Nagoya 467-8601, Aichi, Japan

2. Experimental Pathology and Tumor Biology, Nagoya City University, Nagoya 467-8601, Aichi, Japan

3. Center of Applied Superconductivity and Energy Research (CASER), Chubu University, 1200 Matsumoto, Kasugai 487-8501, Aichi, Japan

4. College of Bioscience and Biotechnology, Chubu University, 1200 Matsumoto, Kasugai 487-8501, Aichi, Japan

5. Graduate Institute of Applied Science and Technology, National Taiwan University of Science and Technology, Taipei 10607, Taiwan

Abstract

The prognosis of castration-resistant prostate cancer (CRPC) is technically scarce; therefore, a novel treatment for CRPC remains warranted. To this end, hyperthermia (HT) was investigated as an alternative therapy. In this study, the analysis focused on the association between CRPC and heat shock protein nuclear import factor “hikeshi (HIKESHI)”, a factor of heat tolerance. Silencing the HIKESHI expression of 22Rv1 cells (human CRPC cell line) treated with siRNAs inhibited the translocation of heat shock protein 70 from the cytoplasm to the nucleus under heat shock and enhanced the effect of hyperthermia. Moreover, a novel magnetic nanoparticle was developed via binding carbon nanohorn (CNH) and iron oxide nanoparticle (IONP) with 3-aminopropylsilyl (APS). Tumor-bearing model mice implanted with 22 Rv1 cells were examined to determine the effect of magnetic HT (mHT). We locally injected CNH-APS-IONP into the tumor, which was set under an alternative magnetic field and showed that tumor growth in the treatment group was significantly suppressed compared with other groups. This study suggests that HIKESHI silencing enhances the sensitivity of 22Rv1 cells to HT, and CNH-APTES-IONP deserves consideration for mHT.

Funder

JSPS KAKENHI

Grant-in-Aid of Watanabe Foundation

Japanese Foundation for Prostate Research

Publisher

MDPI AG

Subject

Pharmaceutical Science

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