硼替佐米的治疗效果与多发性骨髓瘤细胞中FGFR3的表达相关。
Bortezomib therapeutic effect is associated with expression of FGFR3 in multiple myeloma cells.
作者信息
Guan Min, Zhu Lijun, Somlo George, Hughes Alison, Zhou Bingsen, Yen Yun
机构信息
Department of Clinical Molecular Pharmacology, Division of Medical Oncology and Therapeutic Research, City of Hope National Medical Center, Duarte, CA, 91010, USA.
出版信息
Anticancer Res. 2009 Jan;29(1):1-9.
UNLABELLED
The ectopically expressed and deregulated fibroblast growth factor receptor 3 (FGFR3) has been observed in approximately 20% of multiple myeloma (MM) patients. In this study, we investigated whether the therapeutic effect of bortezomib is associated with FGFR3 expression.
MATERIALS AND METHODS
Cell proliferation and apoptosis assays were performed in minimal FGFR3 expressing U266 cells and compared to U266 cells overexpressing FGFR3 wild-type (T-U266), or Y373C (Y-U266) or K650E (K-U266) mutant FGFR3.
RESULTS
Our results suggested cell survival decreases in a dose-dependent manner. Interestingly, expression of FGFR3 protein was similarly dose dependent on bortezomib. It is confirmed the bortezomib-induced apoptotic death is correlated with FGFR3 expression. Furthermore, increased expression of p-STAT3, Mcl-1 and VEGF suggested that bortezomib resistance associated with Y373C mutation and wild-type FGFR3 may be partly mediated through p-STAT3 signaling.
CONCLUSION
Our data indicates that Y373C mutation and wild-type FGFR3 may be associated with bortezomib-related treatment resistance in multiple myeloma.
未标记
在大约20%的多发性骨髓瘤（MM）患者中观察到异位表达且失调的成纤维细胞生长因子受体3（FGFR3）。在本研究中，我们调查了硼替佐米的治疗效果是否与FGFR3表达相关。
材料与方法
在低表达FGFR3的U266细胞中进行细胞增殖和凋亡检测，并与过表达FGFR3野生型（T-U266）、Y373C（Y-U266）或K650E（K-U266）突变型FGFR3的U266细胞进行比较。
结果
我们的结果表明细胞存活率呈剂量依赖性降低。有趣的是，FGFR3蛋白的表达同样呈硼替佐米剂量依赖性。证实硼替佐米诱导的凋亡死亡与FGFR3表达相关。此外，p-STAT3、Mcl-1和VEGF表达增加表明，与Y373C突变和野生型FGFR3相关的硼替佐米耐药可能部分通过p-STAT3信号传导介导。
结论
我们的数据表明，Y373C突变和野生型FGFR3可能与多发性骨髓瘤中硼替佐米相关的治疗耐药有关。
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