Department of Internal Medicine, Seoul National University College of Medicine, Seoul, Republic of Korea.
Cancer Lett. 2010 Dec 18;299(1):22-8. doi: 10.1016/j.canlet.2010.07.020. Epub 2010 Aug 19.
We evaluated RAD001, an inhibitor of the mammalian target of rapamycin (mTOR) in human gastric cancer cell lines and determined the molecular mechanisms. RAD001 has marked growth inhibitory activity against the SNU-1 and SNU-216 cells. It inhibited phosphorylation of mTOR and S6K, and induced G1 cell cycle arrest. Synergistic growth-inhibitory effects in combination with 5-fluorouracil (5-FU) was identified. Furthermore, RAD001 conferred sensitivity to 5-FU-resistant cell lines by downregulating thymidylate synthase (TS). In conclusion, RAD001 showed growth inhibitory activity against gastric cancer cells and acted synergistically with cytotoxic agents such as 5-FU by downregulating TS.
我们评估了 RAD001，一种哺乳动物雷帕霉素靶蛋白（mTOR）抑制剂，在人胃癌细胞系中，并确定了其分子机制。RAD001 对 SNU-1 和 SNU-216 细胞具有显著的生长抑制活性。它抑制 mTOR 和 S6K 的磷酸化，并诱导 G1 细胞周期停滞。与 5-氟尿嘧啶（5-FU）联合具有协同的生长抑制作用。此外，RAD001 通过下调胸苷酸合成酶（TS）使 5-FU 耐药细胞系变得敏感。总之，RAD001 对胃癌细胞具有生长抑制活性，并通过下调 TS 与细胞毒性药物如 5-FU 协同作用。
