Lx2-32c, a novel taxane and its antitumor activities in vitro and in vivo
Lx2-32c, a novel taxane and its antitumor activities in vitro and in vivo
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新型紫杉烷Lx2-32c及其体内外抗肿瘤活性
DOI：
10.1016/j.canlet.2008.03.051
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发表时间：
2008-09-08
期刊：
影响因子：
9.7
通讯作者：
Chen, Xiaoguang
中科院分区：
文献类型：
--
作者：
Wang, Hongbo;Li, Hongyan;Chen, Xiaoguang
Lx 2 - 32 c是一种新的紫杉烷衍生物，是三尖杉宁碱的半合成类似物。本实验研究了其体内外抗肿瘤活性。孵育72小时后，Lx 2 - 32 c对各种人肿瘤细胞系具有细胞毒性（IC 50 = 1.7 +/- 1.6 nM）。体外实验表明，紫杉醇能剂量依赖性地促进BGC-823细胞微管蛋白聚合，并诱导微管成束，其作用方式与紫杉醇相似。流式细胞仪检测结果显示，Lx 2 - 32 c作用12 h或24 h后，可引起BGC-823细胞G（2）/M期阻滞，并呈时间和剂量依赖性。此外，我们证明Lx 2 - 32 c对BGC-823（人胃癌）和A549（人非小细胞肺癌）裸鼠移植瘤具有显著的抗肿瘤活性。这些数据表明，Lx 2 - 32 c是一种微管稳定剂，在体外和体内具有显著的抗肿瘤活性。(C)2008爱思唯尔爱尔兰有限公司保留所有权利。
Lx2-32c, a novel taxane derivative, is a semisynthetic analogue from cephalomannine. Its antitumor activity in vivo and in vitro was investigated in this study. Lx2-32c was cytotoxic (IC50 = 1.7 +/- 1.6 nM) to various human tumor cell lines after 72 h incubation. In vitro it enhanced the rate of tubulin polymerization in a dose-dependent manner and induced the bundling of microtubule in BGC-823 cells with the mode similar to that of paclitaxel. As determined by flow cytometry, after either 12 or 24 h exposure, Lx2-32c caused BGC-823 cells G(2)/M phase arrest in a time- and dose-dependent manner. Moreover, we demonstrated that Lx2-32c had significant antitumor activity on BGC-823 (human gastric carcinoma) and A549 (human non-small cell lung carcinoma) xenograft in nude mice. These data suggest that Lx2-32c is a microtubule-stabilizing agent, which has significant antitumor activity in vitro and in vivo. (C) 2008 Elsevier Ireland Ltd. All rights reserved.