Combined γ-Tocotrienol and Erlotinib/Gefitinib Treatment Suppresses Stat and Akt Signaling in Murine Mammary Tumor Cells
Combined γ-Tocotrienol and Erlotinib/Gefitinib Treatment Suppresses Stat and Akt Signaling in Murine Mammary Tumor Cells
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γ-生育三烯酚和厄洛替尼/吉非替尼联合治疗可抑制小鼠乳腺肿瘤细胞中的 Stat 和 Akt 信号传导
DOI：
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发表时间：
2010
期刊：
影响因子：
--
通讯作者：
P. Sylvester
中科院分区：
文献类型：
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作者：
Sunitha V. Bachawal;V. Wali;P. Sylvester
背景：ErbB受体之间的异二聚体协同作用限制了受体酪氨酸激酶抑制剂(TKIs)、厄洛替尼和吉非替尼在癌症治疗中的临床应用。然而，TKI与γ-生育三烯醇联合治疗靶向多个ErbB受体，并显著抑制+SA小鼠乳腺肿瘤细胞的生长。材料和方法：采用四甲基偶氮唑蓝(四甲基偶氮唑蓝)比色法和免疫荧光Ki-67染色检测细胞增殖。Western印迹分析确定对表皮生长因子(EGF)依赖的有丝分裂信号的处理效果。结果：3μMγ-生育三烯醇与0.2 5μ美洛替尼或0.5μM吉非替尼联合作用可显著抑制+SA细胞的生长，降低细胞周期蛋白D1和磷酸化(活性)的pDK1、Akt、STAT3和STAT5水平。结论：γ-tocotrienol与erlotinib或gefitinib联合治疗可阻止ErbB受体异二聚体的协同作用，并抑制+SA小鼠乳腺肿瘤细胞中依赖于EGF的有丝分裂信号。这些发现有力地表明，联合治疗可以显著提高乳腺癌患者的治疗反应性。
Background: Heterodimer cooperation between ErbB receptors has limited clinical usefulness of receptor tyrosine kinase inhibitors (TKIs), erlotinib and gefitinib in the treatment of cancer. However, combination treatment of TKIs with γ-tocotrienol targets multiple ErbB receptors and significantly inhibit +SA murine mammary tumor cell growth. Materials and Methods: Cell proliferation was determined by tetrazolium (MTT) assay and immunofluorescent Ki-67 staining. Western blot analysis was used to determine treatment effects on epidermal growth factor (EGF)-dependent mitogenic signaling. Results: Combined treatment of 3 μM γ-tocotrienol with 0.25 μM erlotinib or 0.5 μM gefitinib significantly inhibited +SA cell growth and reduced cyclin D1 and phosphorylated (active) Pdk-1, Akt, Stat3 and Stat5 levels. Conclusion: Combined treatment of γ-tocotrienol with erlotinib or gefitinib prevents ErbB receptor heterodimer cooperation and inhibits EGF-dependent mitogenic signaling in +SA murine mammary tumor cells. These findings strongly suggest that combination treatment may significantly improve therapeutic responsiveness in breast cancer patients.
表皮生长因子诱导的小鼠乳腺上皮细胞体外增殖的脂肪酸调节。
影响因子：
3.7
作者：
Sylvester,PW;Birkenfeld,HP;Hosick,HL;Briski,KP
通讯作者：
Briski,KP