Class III β-tubulin overexpression induces chemoresistance to eribulin in a leiomyosarcoma cell line

Kenichiro Yahiro, Yoshihiro Matsumoto, Jun-Ichi Fukushi, Kenichi Kawaguchi, Makoto Endo, Nokitaka Setsu, Keiichiro Iida, Suguru Fukushima, Makoto Nakagawa, Atsushi Kimura, Yoshinao Oda, Yasuharu Nakashima

Research output: Contribution to journalArticle

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Abstract

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.

Original languageEnglish
Article number8987568
JournalAnalytical Cellular Pathology
Volume2018
DOIs
Publication statusPublished - Jan 1 2018

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eribulin
Leiomyosarcoma
Tubulin
Cell Line
Sarcoma
P-Glycoprotein
Microtubules
Pharmaceutical Preparations

All Science Journal Classification (ASJC) codes

  • Pathology and Forensic Medicine
  • Molecular Medicine
  • Cell Biology
  • Cancer Research

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Class III β-tubulin overexpression induces chemoresistance to eribulin in a leiomyosarcoma cell line. / Yahiro, Kenichiro; Matsumoto, Yoshihiro; Fukushi, Jun-Ichi; Kawaguchi, Kenichi; Endo, Makoto; Setsu, Nokitaka; Iida, Keiichiro; Fukushima, Suguru; Nakagawa, Makoto; Kimura, Atsushi; Oda, Yoshinao; Nakashima, Yasuharu.

In: Analytical Cellular Pathology, Vol. 2018, 8987568, 01.01.2018.

Research output: Contribution to journalArticle

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AU - Endo, Makoto

AU - Setsu, Nokitaka

AU - Iida, Keiichiro

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AU - Kimura, Atsushi

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