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Class III β-Tubulin Overexpression Induces Chemoresistance to Eribulin in a Leiomyosarcoma Cell Line
Eribulin is a new drug to treat soft tissue sarcoma (STS) that exerts antitumor activity by binding to microtubules. The prognosis of STS is poor, and eribulin is expected to improve the treatment outcome. We observed several cases that exhibited resistance to eribulin and developed an eribulin-resi...
Autores principales: | , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Hindawi
2018
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6033248/ https://www.ncbi.nlm.nih.gov/pubmed/30034996 http://dx.doi.org/10.1155/2018/8987568 |
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author | Yahiro, Kenichiro Matsumoto, Yoshihiro Fukushi, Jun-ichi Kawaguchi, Ken-ichi Endo, Makoto Setsu, Nokitaka IIda, Keiichiro Fukushima, Suguru Nakagawa, Makoto Kimura, Atsushi Oda, Yoshinao Nakashima, Yasuharu |
author_facet | Yahiro, Kenichiro Matsumoto, Yoshihiro Fukushi, Jun-ichi Kawaguchi, Ken-ichi Endo, Makoto Setsu, Nokitaka IIda, Keiichiro Fukushima, Suguru Nakagawa, Makoto Kimura, Atsushi Oda, Yoshinao Nakashima, Yasuharu |
author_sort | Yahiro, Kenichiro |
collection | PubMed |
description | Eribulin is a new drug to treat soft tissue sarcoma (STS) that exerts antitumor activity by binding to microtubules. The prognosis of STS is poor, and eribulin is expected to improve the treatment outcome. We observed several cases that exhibited resistance to eribulin and developed an eribulin-resistant leiomyosarcoma cell line to investigate the mechanism of resistance. The IC50 of eribulin was 125 times higher in the resistant cell line than in the parental cell line, and eribulin did not induce G2/M arrest in resistant cells. The resistant cell line showed increased expression of MDR1 transcript, but protein levels and functional analysis results were similar to the parental cell line. We found that class III β-tubulin (TUBB3) was overexpressed in the resistant cell line, and siRNA knockdown of TUBB3 partially recovered sensitivity to eribulin. TUBB3 expression in clinical samples varied, suggesting that TUBB3 has the potential to be a biomarker for selection of anticancer drugs and may be a target for overcoming resistance to eribulin. |
format | Online Article Text |
id | pubmed-6033248 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2018 |
publisher | Hindawi |
record_format | MEDLINE/PubMed |
spelling | pubmed-60332482018-07-22 Class III β-Tubulin Overexpression Induces Chemoresistance to Eribulin in a Leiomyosarcoma Cell Line Yahiro, Kenichiro Matsumoto, Yoshihiro Fukushi, Jun-ichi Kawaguchi, Ken-ichi Endo, Makoto Setsu, Nokitaka IIda, Keiichiro Fukushima, Suguru Nakagawa, Makoto Kimura, Atsushi Oda, Yoshinao Nakashima, Yasuharu Anal Cell Pathol (Amst) Research Article Eribulin is a new drug to treat soft tissue sarcoma (STS) that exerts antitumor activity by binding to microtubules. The prognosis of STS is poor, and eribulin is expected to improve the treatment outcome. We observed several cases that exhibited resistance to eribulin and developed an eribulin-resistant leiomyosarcoma cell line to investigate the mechanism of resistance. The IC50 of eribulin was 125 times higher in the resistant cell line than in the parental cell line, and eribulin did not induce G2/M arrest in resistant cells. The resistant cell line showed increased expression of MDR1 transcript, but protein levels and functional analysis results were similar to the parental cell line. We found that class III β-tubulin (TUBB3) was overexpressed in the resistant cell line, and siRNA knockdown of TUBB3 partially recovered sensitivity to eribulin. TUBB3 expression in clinical samples varied, suggesting that TUBB3 has the potential to be a biomarker for selection of anticancer drugs and may be a target for overcoming resistance to eribulin. Hindawi 2018-06-21 /pmc/articles/PMC6033248/ /pubmed/30034996 http://dx.doi.org/10.1155/2018/8987568 Text en Copyright © 2018 Kenichiro Yahiro et al. http://creativecommons.org/licenses/by/4.0/ This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. |
spellingShingle | Research Article Yahiro, Kenichiro Matsumoto, Yoshihiro Fukushi, Jun-ichi Kawaguchi, Ken-ichi Endo, Makoto Setsu, Nokitaka IIda, Keiichiro Fukushima, Suguru Nakagawa, Makoto Kimura, Atsushi Oda, Yoshinao Nakashima, Yasuharu Class III β-Tubulin Overexpression Induces Chemoresistance to Eribulin in a Leiomyosarcoma Cell Line |
title | Class III β-Tubulin Overexpression Induces Chemoresistance to Eribulin in a Leiomyosarcoma Cell Line |
title_full | Class III β-Tubulin Overexpression Induces Chemoresistance to Eribulin in a Leiomyosarcoma Cell Line |
title_fullStr | Class III β-Tubulin Overexpression Induces Chemoresistance to Eribulin in a Leiomyosarcoma Cell Line |
title_full_unstemmed | Class III β-Tubulin Overexpression Induces Chemoresistance to Eribulin in a Leiomyosarcoma Cell Line |
title_short | Class III β-Tubulin Overexpression Induces Chemoresistance to Eribulin in a Leiomyosarcoma Cell Line |
title_sort | class iii β-tubulin overexpression induces chemoresistance to eribulin in a leiomyosarcoma cell line |
topic | Research Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6033248/ https://www.ncbi.nlm.nih.gov/pubmed/30034996 http://dx.doi.org/10.1155/2018/8987568 |
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