Nagoya University Graduate School of Medicine, Department of Gastroenterological Surgery (Surgery II), Nagoya 466-8550, Japan.
Cancer Lett. 2013 May 1;331(2):220-9. doi: 10.1016/j.canlet.2013.01.004. Epub 2013 Jan 20.
We studied the effect of everolimus, an inhibitor of the mammalian target of rapamycin (mTOR) on human gastric cancer cell lines. Cell proliferation in 3 of 8 cell lines was effectively inhibited by everolimus. Basal phosphorylation level of 4E-BP1 (T37/46, T70) was significantly higher in everolimus-sensitive cells than in everolimus-resistant cells. In subcutaneous xenograft model, immunohistochemistry analysis revealed that everolimus-sensitive cells expressed high levels of phospho-4E-BP1 (T37/46). In conclusion, phosphorylation of 4E-BP1 may be a predictive biomarker of everolimus sensitivity in gastric cancer.
我们研究了哺乳动物雷帕霉素靶蛋白(mTOR)抑制剂依维莫司对人胃癌细胞系的影响。依维莫司有效抑制了 8 个人胃癌细胞系中的 3 种细胞增殖。依维莫司敏感细胞的 4E-BP1(T37/46,T70)的基础磷酸化水平明显高于依维莫司耐药细胞。在皮下异种移植模型中,免疫组化分析显示,依维莫司敏感细胞表达高水平的磷酸化 4E-BP1(T37/46)。总之,4E-BP1 的磷酸化可能是胃癌中依维莫司敏感性的预测性生物标志物。