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CAS No. : 119413-54-6
MCE 国际站:Topotecan Hydrochloride
产品活性:Topotecan Hydrochloride (SKF 104864A Hydrochloride) 是具有抗癌活性的 拓扑异构酶I 抑制剂。
研究领域:Cell Cycle/DNA Damage | Autophagy | Apoptosis
作用靶点:Topoisomerase | Autophagy | Apoptosis
结构分类:生物碱 | 喹啉类生物碱 | 酚类 | 单酚类 | 结构分类
来源:植物 | 蓝果树科 | 喜树
In Vitro: Topotecan Hydrochloride (SKF 104864A Hydrochloride) obviously inhibits the proliferation of not only human glioma cells but also glioma stem cells (GSCs) in a dose- and time-dependent manner. According to the IC50 values at 24 h, 3 μM of Topotecan Hydrochloride is selected as the optimal administration concentration. In addition, Topotecan Hydrochloride induces cell cycle arrest in G0/G1 and S phases and promoted apoptosis. Results show that cell viability is inhibited by Topotecan Hydrochloride in a dose-dependent manner. 2, 20 and 40 μM of Topotecan Hydrochloride obviously inhibits the cell viability compared with the control groups. The IC50 values of Topotecan Hydrochloride at 24 h are 2.73±0.25 μM of U251 cells, 2.95±0.23 μM of U87 cells, 5.46±0.41 μM of GSCs-U251 and 5.95±0.24 μM of GSCs-U87. Thus 3 μM of Topotecan Hydrochloride is selected as the optimal administration concentration in the subsequent experiments.
In Vivo: NUB-7 metastatic model, the animals belonging to all the 4 groups are sacrificed after 14 days of treatment. Compared with the control, Low dose metronomic (LDM) Topotecan Hydrochloride and TP+Pazopanib (PZ) liver weights are significantly lower in TP+PZ-treated animals, compared with PZ. Microscopic tumors are visible in the livers of mice belonging to all the groups except TP+PZ confirming the ability of Topotecan Hydrochloride+PZ to control liver metastasis. In a previous dose-response study, the daily dose of oral metronomic Topotecan Hydrochloride (0.5, 1.0, and 1.5 mg/kg) causes greater reduction in microvascular density compared with weekly maximum-tolerated dose regimen (7.5 and 15 mg/kg) in an ovarian cancer model, but the mice treated with 1.5 mg/kg daily, oral Topotecan Hydrochloride show decreased food intake, and a lesser antitumor effect.
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