Zhang Li, Davis Jeffrey S, Zelivianski Stanislav, Lin Fen-Fen, Schutte Rachel, Davis Thomas L, Hauke Ralph, Batra Surinder K, Lin Ming-Fong
Department of Biochemistry and Molecular Biology, University of Nebraska Medical Center, Omaha, 68198-5870, USA.
Cancer Lett. 2009 Nov 18;285(1):58-65. doi: 10.1016/j.canlet.2009.04.041. Epub 2009 May 24.
We examined the efficacy of combination treatments utilizing cytotoxic drugs plus inhibitors to members of the ErbB-ERK signal pathway in human prostate cancer (PCa) LNCaP C-81 cells. Under an androgen-reduced condition, 50nM gemcitabine caused about 40% growth suppression on C-81 cells. Simultaneous treatment of gemcitabine plus 10microM AG825 produced 60% suppression (p<0.03); while, 85% growth inhibition (p<0.02) was seen if AG825 was added to gemcitabine-treated cells after a 24h-interval. Our data thus showed that in androgen-reduced conditions, inhibition of ErbB-2 increases the cytotoxic efficacy of gemcitabine in PCa cells. This finding has significant implications in the choice of drugs for combination therapy as well as the order of administration for treating cancer patients.
我们研究了在人前列腺癌（PCa）LNCaP C-81细胞中，使用细胞毒性药物加ErbB-ERK信号通路成员抑制剂的联合治疗效果。在雄激素降低的条件下，50nM吉西他滨对C-81细胞产生约40%的生长抑制。吉西他滨与10μM AG825同时处理产生60%的抑制作用（p<0.03）；而如果在24小时间隔后将AG825添加到经吉西他滨处理的细胞中，则可见85%的生长抑制（p<0.02）。因此，我们的数据表明，在雄激素降低的条件下，抑制ErbB-2可增加吉西他滨在PCa细胞中的细胞毒性功效。这一发现对联合治疗药物的选择以及癌症患者治疗的给药顺序具有重要意义。
