TY - JOUR
T1 - Class III β-tubulin overexpression induces chemoresistance to eribulin in a leiomyosarcoma cell line
AU - Yahiro, Kenichiro
AU - Matsumoto, Yoshihiro
AU - Fukushi, Jun ichi
AU - Kawaguchi, Ken ichi
AU - Endo, Makoto
AU - Setsu, Nokitaka
AU - IIda, Keiichiro
AU - Fukushima, Suguru
AU - Nakagawa, Makoto
AU - Kimura, Atsushi
AU - Oda, Yoshinao
AU - Nakashima, Yasuharu
N1 - Funding Information:
This work was supported in part by Grants-in-Aid for Young Scientists (A 26713046 and B 17k16696) from the Japan Society for the Promotion of Science and a Grant from Japan Orthopaedics and Traumatology Research Foundation Inc. (no. 332).
PY - 2018
Y1 - 2018
N2 - 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.
AB - 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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U2 - 10.1155/2018/8987568
DO - 10.1155/2018/8987568
M3 - Article
C2 - 30034996
AN - SCOPUS:85055614201
VL - 2018
JO - Analytical Cellular Pathology
JF - Analytical Cellular Pathology
SN - 2210-7177
M1 - 8987568
ER -