Alami N, Paterson J, Belanger S, Juste S, Grieshaber C K, Leyland-Jones B
Department of Oncology, McGill University, Montreal, QC, Canada.
J Chemother. 2007 Oct;19(5):546-53. doi: 10.1179/joc.2007.19.5.546.
The aim of this study was to investigate the antiproliferative effects of C-1311 (Symadex), a member of the imidazoacridinone family, in human colorectal cancer cells. In the in vitro screen, C-1311 led to the most prominent growth inhibition in HT29, HCT116, and COLO205 cell lines when compared to oxaliplatin, CPT-11, DFUR, 5-FU and capecitabine. The GI(50)values for C-1311 ranged from 0.12 to 0.83 microM and the TGI concentrations (resulting in total growth inhibition) were 6- to 13-fold lower than those of other agents. In the hollow fiber assay in vivo, C-1311 caused 77% growth inhibition of HT29 in the intraperitoneal site as compared to paclitaxel (17% growth inhibition). In the subcutaneous site, C-1311 produced 57% growth inhibition while paclitaxel showed no cell growth inhibition effects. This unique cytotoxicity profile of C-1311 warrants further investigation and supports its clinical development in colon cancer patients. Symadex (C-1311) is currently in phase 2 clinical trials.
本研究旨在探讨咪唑并吖啶酮家族成员C-1311（Symadex）对人结肠癌细胞的抗增殖作用。在体外筛选中，与奥沙利铂、伊立替康、去氧氟尿苷、5-氟尿嘧啶和卡培他滨相比，C-1311在HT29、HCT116和COLO205细胞系中导致最显著的生长抑制。C-1311的GI(50)值范围为0.12至0.83微摩尔，其TGI浓度（导致完全生长抑制）比其他药物低6至13倍。在体内中空纤维试验中，与紫杉醇（生长抑制率17%）相比，C-1311在腹腔部位使HT29生长抑制率达到77%。在皮下部位，C-1311产生了57% 的生长抑制，而紫杉醇未显示细胞生长抑制作用。C-1311这种独特的细胞毒性特征值得进一步研究，并支持其在结肠癌患者中的临床开发。Symadex（C-1311）目前正处于2期临床试验阶段。
