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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...

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Autores principales: 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
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Hindawi 2018
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.
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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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