Surgical Oncology, Gifu University School of Medicine, 1-1, Yanagido, Gifu, 501-1194, Japan.
Anticancer Res. 2010 Jul;30(7):2625-30.
To determine a novel chemotherapeutic concept for hormone receptor-negative and HER2-positive breast cancer, a high progression form of the disease for which treatment has been difficult. A combination therapy of 5-fluorouracil (5-FU) with rapamycin (Rap) was examined.
The growth inhibitory effect of treatment was evaluated by an MTT assay and cellular signal/apoptotic pathways were investigated by Western blotting and Hoechst 33342 staining.
Rap was shown to induce an inhibitory effect on the phosphorylation of mTOR and p70S6K. The expression of thymidine synthase (TS) was decreased by Rap. The addition of 5-FU to Rap was found to increase cell death. The Hoechst 33342 assay showed that apoptosis was increased by the combination of 5-FU and Rap in comparison to 5FU alone.
5-FU is more effective in combination with the TS-reducing action of Rap, even for highly HER2-expressing breast cancer cells.
确定一种新的化疗概念，用于治疗激素受体阴性和 HER2 阳性乳腺癌，这是一种疾病的高进展形式，治疗一直很困难。研究了氟尿嘧啶（5-FU）联合雷帕霉素（Rap）的联合治疗。
通过 MTT 测定评估治疗的生长抑制作用，并通过 Western blot 和 Hoechst 33342 染色研究细胞信号/凋亡途径。
Rap 被证明能抑制 mTOR 和 p70S6K 的磷酸化。Rap 降低胸苷酸合成酶（TS）的表达。发现 5-FU 与 Rap 联合使用可增加细胞死亡。Hoechst 33342 检测表明，与单独使用 5-FU 相比，5-FU 和 Rap 的联合使用可增加细胞凋亡。
即使对于高度表达 HER2 的乳腺癌细胞，5-FU 与 Rap 降低 TS 作用的联合使用更有效。
