Impact of oxygen status on 10B-BPA uptake into human glioblastoma cells, referring to significance in boron neutron capture therapy.

Abstract

Boron neutron capture therapy (BNCT) can potentially deliver high linear energy transfer particles to tumor cells without causing severe damage to surrounding normal tissue, and may thus be beneficial for cases with characteristics of infiltrative growth, which need a wider irradiation field, such as glioblastoma multiforme. Hypoxia is an important factor contributing to resistance to anticancer therapies such as radiotherapy and chemotherapy. In this study, we investigated the impact of oxygen status on 10B uptake in glioblastoma cells in vitro in order to evaluate the potential impact of local hypoxia on BNCT. T98G and A172 glioblastoma cells were used in the present study, and we examined the influence of oxygen concentration on cell viability, mRNA expression of L-amino acid transporter 1 (LAT1), and the uptake amount of 10B-BPA. T98G and A172 glioblastoma cells became quiescent after 72 h under 1% hypoxia but remained viable. Uptake of 10B-BPA, which is one of the agents for BNCT in clinical use, decreased linearly as oxygen levels were reduced from 20% through to 10%, 3% and 1%. Hypoxia with <10% O2 significantly decreased mRNA expression of LAT1 in both cell lines, indicating that reduced uptake of 10B-BPA in glioblastoma in hypoxic conditions may be due to reduced expression of this important transporter protein. Hypoxia inhibits 10B-BPA uptake in glioblastoma cells in a linear fashion, meaning that approaches to overcoming local tumor hypoxia may be an effective method of improving the success of BNCT treatment.

• Authors: Yuki Wada, Katsumi Hirose, Takaomi Harada, Mariko Sato, Tsubasa Watanabe, Akira Anbai, Manabu Hashimoto, Yoshihiro Takai
• Journal: Journal of radiation research (J Radiat Res) Vol. 59 Issue 2 Pg. 122-128 (Mar 01 2018) ISSN: 1349-9157 [Electronic] England
• PMID: 29315429 (Publication Type: Journal Article)

Chemical References

• Adaptor Proteins, Signal Transducing
• Boron Compounds
• LAT2 protein, human
• Large Neutral Amino Acid-Transporter 1
• RNA, Messenger
• Phenylalanine
• Oxygen
• 4-boronophenylalanine

Topics

• Adaptor Proteins, Signal Transducing (genetics, metabolism)
• Boron Compounds (therapeutic use)
• Boron Neutron Capture Therapy
• Cell Hypoxia (radiation effects)
• Cell Line, Tumor
• Cell Proliferation (radiation effects)
• Cell Survival (radiation effects)
• Gene Expression Regulation, Neoplastic
• Glioblastoma (genetics, pathology, radiotherapy)
• Humans
• Large Neutral Amino Acid-Transporter 1 (genetics, metabolism)
• Oxygen (metabolism)
• Phenylalanine (analogs & derivatives, therapeutic use)
• RNA, Messenger (genetics, metabolism)