In vitro and in vivo suppression of growth of hepatocellular carcinoma cells by albendazole
In vitro and in vivo suppression of growth of hepatocellular carcinoma cells by albendazole
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DOI：
10.1016/s0304-3835(01)00382-2
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发表时间：
2001-04-10
期刊：
影响因子：
9.7
通讯作者：
Morris, DL
中科院分区：
文献类型：
--
作者：
Pourgholami, MH;Woon, L;Morris, DL
微管蛋白是药物分子的主要靶点，因此，微管蛋白抑制剂作为用于化疗的抗有丝分裂抗肿瘤剂引起了极大的关注。已经表明，包括阿苯达唑在内的抗寄生虫药的苯并咪唑氨基甲酸酯基团通过抑制微管蛋白聚合而起作用。在这项研究中，阿苯达唑进行了测试，对一系列的人类，大鼠和小鼠肝细胞癌（HCC）细胞的培养物和在裸鼠体内对人类SKHEP-1肿瘤生长。阿苯达唑诱导的[H-3]胸苷掺入的剂量依赖性抑制在所有的细胞系检查和SKHEP-1细胞的细胞数量急剧下降。阿苯达唑的抑制作用在100 nM浓度下是明显的，并且在1000 nM浓度下，与对照相比，在所有检查的细胞系中增殖被抑制超过80%，而HepG 2、Hep 3B和SKHEP-1的增殖被抑制超过90%。细胞周期分析显示，根据使用的剂量，阿苯达唑可以将SKHEP-1细胞阻滞在周期的G 0-G1（250 nM）和G2-M（1000 nM）期。皮下接种SKHEP-1的裸鼠的阿苯达唑治疗（每天口服300 mg/kg，持续20天）导致肿瘤生长的显著抑制。这些肿瘤的免疫组化分析显示，与对照组相比，阿苯达唑治疗的肿瘤具有较低的生长分数。这些结果表明，阿苯达唑强烈抑制肝癌细胞在体外和体内的增殖。(C)2001爱思唯尔科学爱尔兰有限公司保留所有权利。
Tubulin protein is a major target of drug molecules, and consequently, tubulin inhibitors have attracted great attention as antimitotic antitumor agents for chemotherapeutic use. It has been shown that, the benzimidazole carbamate group of antiparasitics including albendazole act by inhibiting tubulin polymerization. In this study, albendazole was tested in culture against a range of human, rat and mice hepatocellular carcinoma (HCC) cells and in vivo against human SKHEP-1 tumor growth in nude mice. Albendazole induced a dose-dependent inhibition of [H-3]thymidine incorporation in all cell lines examined and a dramatic decline in cell numbers in SKHEP-1 cells. The inhibitory effect of albendazole was evident at the 100 nM concentration and at 1000 nM, proliferation in all cell lines examined was inhibited by more than 80%, while, proliferation of HepG2, Hep3B and SKHEP-1 were suppressed by more than 90%, compared to control. Cell cycle analysis revealed that, depending on the dose employed, albendazole can arrest SKHEP-1 cells at both G0-G1 (250 nM) and G2-M (1000 nM) phases of the cycle. Albendazole treatment (300 mg/kg per day oral for 20 days) of nude mice inoculated subcutaneously with SKHEP-1, led to profound suppression of tumor growth. Immunohistochemical analysis of these tumors revealed that compared to control, those treated with albendazole have lower growth fractions. These findings demonstrate that albendazole strongly suppresses both in vitro and in vivo proliferation of HCC cells. (C) 2001 Elsevier Science Ireland Ltd. All rights reserved.