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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| Format: | Article |
| Language: | English |
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Wiley
2018-01-01
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| Series: | Analytical Cellular Pathology |
| Online Access: | http://dx.doi.org/10.1155/2018/8987568 |
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| author | Kenichiro Yahiro Yoshihiro Matsumoto Jun-ichi Fukushi Ken-ichi Kawaguchi Makoto Endo Nokitaka Setsu Keiichiro IIda Suguru Fukushima Makoto Nakagawa Atsushi Kimura Yoshinao Oda Yasuharu Nakashima |
| author_facet | Kenichiro Yahiro Yoshihiro Matsumoto Jun-ichi Fukushi Ken-ichi Kawaguchi Makoto Endo Nokitaka Setsu Keiichiro IIda Suguru Fukushima Makoto Nakagawa Atsushi Kimura Yoshinao Oda Yasuharu Nakashima |
| author_sort | Kenichiro Yahiro |
| collection | DOAJ |
| 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 | Article |
| id | doaj-art-685608d714b54d85867409d5e1b41ca1 |
| institution | Kabale University |
| issn | 2210-7177 2210-7185 |
| language | English |
| publishDate | 2018-01-01 |
| publisher | Wiley |
| record_format | Article |
| series | Analytical Cellular Pathology |
| spelling | doaj-art-685608d714b54d85867409d5e1b41ca12025-02-03T01:28:14ZengWileyAnalytical Cellular Pathology2210-71772210-71852018-01-01201810.1155/2018/89875688987568Class III β-Tubulin Overexpression Induces Chemoresistance to Eribulin in a Leiomyosarcoma Cell LineKenichiro Yahiro0Yoshihiro Matsumoto1Jun-ichi Fukushi2Ken-ichi Kawaguchi3Makoto Endo4Nokitaka Setsu5Keiichiro IIda6Suguru Fukushima7Makoto Nakagawa8Atsushi Kimura9Yoshinao Oda10Yasuharu Nakashima11Department of Orthopaedic Surgery, Graduate School of Medical Sciences, Kyushu University, 3-1-1 Maidashi, Higashi-ku, Fukuoka City 812-8582, JapanDepartment of Orthopaedic Surgery, Graduate School of Medical Sciences, Kyushu University, 3-1-1 Maidashi, Higashi-ku, Fukuoka City 812-8582, JapanDepartment of Orthopaedic Surgery, Graduate School of Medical Sciences, Kyushu University, 3-1-1 Maidashi, Higashi-ku, Fukuoka City 812-8582, JapanDepartment of Orthopaedic Surgery, Graduate School of Medical Sciences, Kyushu University, 3-1-1 Maidashi, Higashi-ku, Fukuoka City 812-8582, JapanDepartment of Orthopaedic Surgery, Graduate School of Medical Sciences, Kyushu University, 3-1-1 Maidashi, Higashi-ku, Fukuoka City 812-8582, JapanDepartment of Orthopaedic Surgery, Graduate School of Medical Sciences, Kyushu University, 3-1-1 Maidashi, Higashi-ku, Fukuoka City 812-8582, JapanDepartment of Orthopaedic Surgery, Graduate School of Medical Sciences, Kyushu University, 3-1-1 Maidashi, Higashi-ku, Fukuoka City 812-8582, JapanDepartment of Orthopaedic Surgery, Graduate School of Medical Sciences, Kyushu University, 3-1-1 Maidashi, Higashi-ku, Fukuoka City 812-8582, JapanDepartment of Orthopaedic Surgery, Graduate School of Medical Sciences, Kyushu University, 3-1-1 Maidashi, Higashi-ku, Fukuoka City 812-8582, JapanDepartment of Orthopaedic Surgery, Graduate School of Medical Sciences, Kyushu University, 3-1-1 Maidashi, Higashi-ku, Fukuoka City 812-8582, JapanDepartment of Anatomic Pathology, Pathological Sciences, Graduate School of Medical Sciences, Kyushu University, Fukuoka, JapanDepartment of Orthopaedic Surgery, Graduate School of Medical Sciences, Kyushu University, 3-1-1 Maidashi, Higashi-ku, Fukuoka City 812-8582, JapanEribulin 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.http://dx.doi.org/10.1155/2018/8987568 |
| spellingShingle | Kenichiro Yahiro Yoshihiro Matsumoto Jun-ichi Fukushi Ken-ichi Kawaguchi Makoto Endo Nokitaka Setsu Keiichiro IIda Suguru Fukushima Makoto Nakagawa Atsushi Kimura Yoshinao Oda Yasuharu Nakashima Class III β-Tubulin Overexpression Induces Chemoresistance to Eribulin in a Leiomyosarcoma Cell Line Analytical Cellular Pathology |
| 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 |
| url | http://dx.doi.org/10.1155/2018/8987568 |
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