Bufalin attenuates the stage and metastatic potential of hepatocellular carcinoma in nude mice.
Bufalin attenuates the stage and metastatic potential of hepatocellular carcinoma in nude mice.
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蟾蜍灵减轻裸鼠肝细胞癌的分期和转移潜力
DOI：
10.1186/1479-5876-12-57
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发表时间：
2014-02-28
影响因子：
7.4
通讯作者：
Wu WZ
中科院分区：
文献类型：
--
作者：
Zhang ZJ;Yang YK;Wu WZ
背景晚期肝细胞癌（HCC）患者肿瘤生长和转移显著。在这里，我们调查蟾毒灵治疗肝癌，这表现出在许多肿瘤细胞株的抗肿瘤活性。方法在我们的实验中，HCCLM 3-R细胞注射到裸鼠皮下，形成皮下人肝癌肿瘤，植入肝脏，建立原位移植瘤模型。蟾蜍灵以1或1.5 mg/kg腹腔注射。将LY 294002（100 mg/kg）（一种有效的Akt抑制剂，其降低HCCLM 3细胞系中的pAkt水平）每周三次腹膜内注射到一组中。对照组注射等体积生理盐水。体视显微镜观察肝、肺组织形态学改变，TUNEL染色检测细胞凋亡率，免疫组化检测AKT/GSK 3 β/β-catenin/E-cadherin信号通路相关蛋白的表达结果蟾蜍灵高剂量组与对照组相比，在控制中。蟾毒灵处理组原位移植瘤组织坏死，最高剂量组凋亡细胞数明显高于对照组。AKT/GSK 3 β/β-catenin/E-cadherin信号通路相关蛋白在肿瘤组织中的表达有一定的变化，且与蟾蜍灵剂量有关。LY 294002治疗组中观察到类似的结果。ConclusionBased on上述，可以得出结论，蟾毒灵具有显着的抗肿瘤活性，并降低了人肝癌原位移植瘤模型的转移潜力。蟾蜍灵抑制AKT/GSK 3 β/β-catenin/E-cadherin信号通路可能对晚期HCC患者具有治疗作用。
BackgroundAdvanced hepatocellular carcinoma (HCC) patients undergo significant tumor growth and metastasis. Here, we investigated bufalin for treating HCC, which exhibits anti-tumor activities in many tumor cell lines.MethodIn our experiment, HCCLM3-R cells were injected into nude mice to form subcutaneous human HCC tumors that were implanted into the liver to establish orthotopic transplantation tumor models. Bufalin was injected intraperitoneally at 1 or 1.5 mg/kg. LY294002 (100 mg/kg), a potent inhibitor of Akt which reduced the levels of pAkt in HCCLM3 cell lines, was injected intraperitoneally into one group thrice weekly. The control was injected with an equal volume of saline. Morphological alterations were evaluated in the liver and lung by stereomicroscopy, the apoptotic rate was measured by TUNEL staining, and expression of AKT/GSK3β/β-catenin/E-cadherin signaling pathway-related proteins was detected by immunohistochemistry (IHC) and western blot analysis.ResultsThese results suggested that the sizes and qualities of orthotopic transplanted tumors as well as pulmonary metastasis decreased markedly at the highest bufalin dose compared with that in the control. Orthotopic transplanted tumor tissues were necrotic in bufalin-treated groups and the apoptotic cell number was markedly higher at the highest bufalin dose compared with that in the control. Certain changes of expression of AKT/GSK3β/β-catenin/E-cadherin signaling pathway-related proteins were in tumor tissues, which were related to the bufalin dose. Similar results were observed in the LY294002-treated group.ConclusionBased on the above, one can draw conclusions that bufalin has significant anti-tumor activities and reduces the metastatic potential in an orthotopic transplantation tumor model of human HCC. Inhibition of AKT/GSK3β/β-catenin/E-cadherin signaling pathways by bufalin may show therapeutic effects in advanced HCC patients.
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