Class III β-Tubulin Overexpression Induces Chemoresistance to Eribulin in a Leiomyosarcoma Cell Line.
Class III β-Tubulin Overexpression Induces Chemoresistance to Eribulin in a Leiomyosarcoma Cell Line.
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DOI：
10.1155/2018/8987568
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发表时间：
2018
期刊：
影响因子：
--
通讯作者：
Nakashima Y
中科院分区：
文献类型：
--
作者：
Yahiro K;Matsumoto Y;Fukushi JI;Kawaguchi KI;Endo M;Setsu N;IIda K;Fukushima S;Nakagawa M;Kimura A;Oda Y;Nakashima Y
艾日布林是一种治疗软组织肉瘤的新药，通过与微管结合发挥抗肿瘤活性。STS的预后差，艾日布林有望改善治疗结果。我们观察了几例对艾日布林耐药的病例，并建立了一个对艾日布林耐药的平滑肌肉瘤细胞系，以探讨耐药的机制。艾日布林在耐药细胞系中的IC 50比在亲本细胞系中高125倍，并且艾日布林在耐药细胞中不诱导G2/M期阻滞。耐药细胞系显示MDR 1转录本表达增加，但蛋白水平和功能分析结果与亲本细胞系相似。我们发现III类β-微管蛋白（TUBB 3）在耐药细胞系中过表达，并且TUBB 3的siRNA敲除部分恢复了对艾日布林的敏感性。TUBB 3在临床样品中的表达变化，表明TUBB 3有可能成为选择抗癌药物的生物标志物，并可能成为克服艾日布林耐药性的靶点。
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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影响因子：
3.3
作者：
Hinsch, Andrea;Chaker, Aref;Jacobsen, Frank
通讯作者：
Jacobsen, Frank
影响因子：
2.4
作者：
Kawai A;Araki N;Naito Y;Ozaki T;Sugiura H;Yazawa Y;Morioka H;Matsumine A;Saito K;Asami S;Isu K
通讯作者：
Isu K
影响因子：
2.9
作者：
Lebok P;Öztürk M;Heilenkötter U;Jaenicke F;Müller V;Paluchowski P;Geist S;Wilke C;Burandt E;Lebeau A;Wilczak W;Krech T;Simon R;Sauter G;Quaas A
通讯作者：
Quaas A
影响因子：
--
作者：
Oba T;Izumi H;Ito KI
通讯作者：
Ito KI
影响因子：
20.4
作者：
Koh, Youngil;Jang, Bogun;Bang, Yung-Jue
通讯作者：
Bang, Yung-Jue