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A single high-dose irradiation changes accumulation of methotrexate and gene expression levels of SLC and ABC transporters in cancer cells
Chemoradiotherapy is frequently used to treat cancer. Stereotactic body radiotherapy (SBRT) is a single high-dose radiotherapy used to treat a variety of cancers. The anticancer drug methotrexate (MTX) shows affinity for solute carrier (SLC) and ATP-binding cassette (ABC) transporters. This study in...
Autores principales: | , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Frontiers Media S.A.
2023
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9874220/ https://www.ncbi.nlm.nih.gov/pubmed/36712667 http://dx.doi.org/10.3389/fphar.2022.1069321 |
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author | Sato, Kakeru Seki, Tatsuya Mizutani, Asuka Muranaka, Yuka Hirota, Shiho Nishi, Kodai Yamazaki, Kana Nishii, Ryuichi Nakanishi, Takeo Tamai, Ikumi Kawai, Keiichi Kobayashi, Masato |
author_facet | Sato, Kakeru Seki, Tatsuya Mizutani, Asuka Muranaka, Yuka Hirota, Shiho Nishi, Kodai Yamazaki, Kana Nishii, Ryuichi Nakanishi, Takeo Tamai, Ikumi Kawai, Keiichi Kobayashi, Masato |
author_sort | Sato, Kakeru |
collection | PubMed |
description | Chemoradiotherapy is frequently used to treat cancer. Stereotactic body radiotherapy (SBRT) is a single high-dose radiotherapy used to treat a variety of cancers. The anticancer drug methotrexate (MTX) shows affinity for solute carrier (SLC) and ATP-binding cassette (ABC) transporters. This study investigated relationships between accumulation of methotrexate and gene expression levels of solute carrier and ATP-binding cassette transporters in cancer cells after a single and high-dose X-ray irradiation. Cancer cell lines were selected from lung and cervical cancer cell line that are commonly used for stereotactic body radiotherapy and effective with methotrexate. We examined expression levels of organic anion-transporting polypeptide (OATP)1B1, OATP1B3, OATP1B7, and organic anion transporter (OAT)1 as solute carrier transporters and multidrug resistance-associated protein (MRP)1 and MRP2 as ATP-binding cassette transporters, using real-time polymerase chain reaction and accumulation of (3)H-MTX in cancer cells after 10-Gy irradiation, assuming stereotactic body radiotherapy. Cells were divided into three groups: Control without irradiation; 4 h after irradiation; and 24 h after irradiation. In control, gene expression levels of OAT1 in all cells was below the limit of measurement. After irradiation, gene expression levels of OATP1B1/1B3/1B7 showed changes in each cell line. Gene expression levels of MRP1/2 tended to increase after irradiation. Gene expression levels of OATP1B1/1B3/1B7 were much lower than those of MRP1/2. Accumulation of (3)H-MTX tended to decrease over time after irradiation. Irradiation of cancer cells thus alters gene expression levels of both solute carrier transporters (OATP1B1/1B3/1B7) and ABC transporters (MRP1/2) and decreases accumulation of (3)H-MTX in cancer cells over time due to elevated expression of MRP1/2. |
format | Online Article Text |
id | pubmed-9874220 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2023 |
publisher | Frontiers Media S.A. |
record_format | MEDLINE/PubMed |
spelling | pubmed-98742202023-01-26 A single high-dose irradiation changes accumulation of methotrexate and gene expression levels of SLC and ABC transporters in cancer cells Sato, Kakeru Seki, Tatsuya Mizutani, Asuka Muranaka, Yuka Hirota, Shiho Nishi, Kodai Yamazaki, Kana Nishii, Ryuichi Nakanishi, Takeo Tamai, Ikumi Kawai, Keiichi Kobayashi, Masato Front Pharmacol Pharmacology Chemoradiotherapy is frequently used to treat cancer. Stereotactic body radiotherapy (SBRT) is a single high-dose radiotherapy used to treat a variety of cancers. The anticancer drug methotrexate (MTX) shows affinity for solute carrier (SLC) and ATP-binding cassette (ABC) transporters. This study investigated relationships between accumulation of methotrexate and gene expression levels of solute carrier and ATP-binding cassette transporters in cancer cells after a single and high-dose X-ray irradiation. Cancer cell lines were selected from lung and cervical cancer cell line that are commonly used for stereotactic body radiotherapy and effective with methotrexate. We examined expression levels of organic anion-transporting polypeptide (OATP)1B1, OATP1B3, OATP1B7, and organic anion transporter (OAT)1 as solute carrier transporters and multidrug resistance-associated protein (MRP)1 and MRP2 as ATP-binding cassette transporters, using real-time polymerase chain reaction and accumulation of (3)H-MTX in cancer cells after 10-Gy irradiation, assuming stereotactic body radiotherapy. Cells were divided into three groups: Control without irradiation; 4 h after irradiation; and 24 h after irradiation. In control, gene expression levels of OAT1 in all cells was below the limit of measurement. After irradiation, gene expression levels of OATP1B1/1B3/1B7 showed changes in each cell line. Gene expression levels of MRP1/2 tended to increase after irradiation. Gene expression levels of OATP1B1/1B3/1B7 were much lower than those of MRP1/2. Accumulation of (3)H-MTX tended to decrease over time after irradiation. Irradiation of cancer cells thus alters gene expression levels of both solute carrier transporters (OATP1B1/1B3/1B7) and ABC transporters (MRP1/2) and decreases accumulation of (3)H-MTX in cancer cells over time due to elevated expression of MRP1/2. Frontiers Media S.A. 2023-01-11 /pmc/articles/PMC9874220/ /pubmed/36712667 http://dx.doi.org/10.3389/fphar.2022.1069321 Text en Copyright © 2023 Sato, Seki, Mizutani, Muranaka, Hirota, Nishi, Yamazaki, Nishii, Nakanishi, Tamai, Kawai and Kobayashi. https://creativecommons.org/licenses/by/4.0/This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms. |
spellingShingle | Pharmacology Sato, Kakeru Seki, Tatsuya Mizutani, Asuka Muranaka, Yuka Hirota, Shiho Nishi, Kodai Yamazaki, Kana Nishii, Ryuichi Nakanishi, Takeo Tamai, Ikumi Kawai, Keiichi Kobayashi, Masato A single high-dose irradiation changes accumulation of methotrexate and gene expression levels of SLC and ABC transporters in cancer cells |
title | A single high-dose irradiation changes accumulation of methotrexate and gene expression levels of SLC and ABC transporters in cancer cells |
title_full | A single high-dose irradiation changes accumulation of methotrexate and gene expression levels of SLC and ABC transporters in cancer cells |
title_fullStr | A single high-dose irradiation changes accumulation of methotrexate and gene expression levels of SLC and ABC transporters in cancer cells |
title_full_unstemmed | A single high-dose irradiation changes accumulation of methotrexate and gene expression levels of SLC and ABC transporters in cancer cells |
title_short | A single high-dose irradiation changes accumulation of methotrexate and gene expression levels of SLC and ABC transporters in cancer cells |
title_sort | single high-dose irradiation changes accumulation of methotrexate and gene expression levels of slc and abc transporters in cancer cells |
topic | Pharmacology |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9874220/ https://www.ncbi.nlm.nih.gov/pubmed/36712667 http://dx.doi.org/10.3389/fphar.2022.1069321 |
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