...
  • 主题
高级搜索  >
历史搜索 清空历史
首页> 外文期刊>Molecular Cancer >Head and neck cancer cells and xenografts are very sensitive to palytoxin: decrease of c-jun n-terminale kinase-3 expression enhances palytoxin toxicity
【24h】

Head and neck cancer cells and xenografts are very sensitive to palytoxin: decrease of c-jun n-terminale kinase-3 expression enhances palytoxin toxicity

机译：头颈癌细胞和异种移植物对palytoxin非常敏感：c-jun n-terminal激酶3的表达降低会增强palytoxin的毒性

获取原文
           
页面导航
  • 摘要
  • 著录项
  • 相似文献
  • 相关主题

摘要

Objectives Palytoxin (PTX), a marine toxin isolated from the Cnidaria (zooanthid) Palythoa caribaeorum is one of the most potent non-protein substances known. It is a very complex molecule that presents both lipophilic and hydrophilic areas. The effect of PTX was investigated in a series of experiments conducted in head and neck squamous cell carcinoma (HNSCC) cell lines and xenografts. Materials and methods Cell viability, and gene expression of the sodium/potassium-transporting ATPase subumit alpha1 (ATP1AL1) and GAPDH were analyzed in HNSCC cells and normal epithelial cells after treatment with PTX using cytotoxicity-, clonogenic-, and enzyme inhibitor assays as well as RT-PCR and Northern Blotting . For xenograft experiments severe combined immunodeficient ( SCID ) mice were used to analyze tumor regression. The data were statistically analyzed using One-Way Annova (SPSS vs20). Results Significant toxic effects were observed in tumor cells treated with PTX (LD50 of 1.5 to 3.5 ng/ml) in contrast to normal cells. In tumor cells PTX affected both the release of LDH and the expression of the sodium/potassium-transporting ATPase subunit alpha1 gene suggesting loss of cellular integrity, primarily of the plasma membrane. Furthermore, strong repression of the c-Jun N-terminal kinase 3 ( JNK3 ) mRNA expression was found in carcinoma cells which correlated with enhanced toxicity of PTX suggesting an essential role of the mitogen activated protein kinase ( MAPK )/JNK signalling cascades pathway in the mechanisms of HNSCC cell resistance to PTX. In mice inoculated with carcinoma cells, injections of PTX into the xenografted tumors resulted within 24 days in extensive tumor destruction in 75% of the treated animals (LD50 of 68?ng/kg to 83?ng/kg) while no tumor regression occurred in control animals. Conclusions These results clearly provide evidence that PTX possesses preferential toxicity for head and neck carcinoma cells and therefore it is worth further studying its impact which may extend our knowledge of the biology of head and neck cancer.
机译：目的Palytoxin（PTX）是一种从猪唇草（zooanthid）分离出来的海洋毒素Palythoa caribaeorum，是已知的最有效的非蛋白质物质之一。它是一个非常复杂的分子，同时具有亲脂性和亲水性区域。在头颈部鳞状细胞癌（HNSCC）细胞系和异种移植物中进行的一系列实验中研究了PTX的作用。材料和方法用PTX处理HNSCC细胞和正常上皮细胞后，还通过细胞毒性，克隆形成和酶抑制剂测定法分析了HNSCC细胞和正常上皮细胞中的细胞生存力以及钠/钾转运ATPase subumit alpha1（ATP1AL1）和GAPDH的基因表达。如RT-PCR和Northern Blotting。对于异种移植实验，使用严重的联合免疫缺陷（SCID）小鼠分析肿瘤的消退。使用单向Annova（SPSS vs20）对数据进行统计分析。结果与正常细胞相比，PTX处理的​​肿瘤细胞（LD50为1.5至3.5 ng / ml）具有明显的毒性作用。在肿瘤细胞中，PTX影响LDH的释放和钠/钾转运ATP酶亚基α1基因的表达，提示细胞完整性（主要是质膜）的丧失。此外，在癌细胞中发现c-Jun N末端激酶3（JNK3）mRNA表达的强烈抑制与PTX的毒性增强有关，提示丝裂原活化蛋白激酶（MAPK）/ JNK信号级联途径的重要作用。 HNSCC细胞对PTX耐药的机制。在接种了癌细胞的小鼠中，向异种移植肿瘤中注射PTX在24天内导致75％的被治疗动物发生了广泛的肿瘤破坏（LD50为68？ng / kg至83？ng / kg），而在2007年没有发生肿瘤消退。控制动物。结论这些结果清楚地证明了PTX对头颈癌细胞具有优先毒性，因此值得进一步研究其影响，这可能会扩展我们对头颈癌生物学的认识。

著录项

相似文献

  • 外文文献
  • 中文文献
  • 专利
获取原文

客服邮箱：kefu@zhangqiaokeyan.com

京公网安备：11010802029741号 ICP备案号：京ICP备15016152号-6 六维联合信息科技 (北京) 有限公司©版权所有

  • 客服微信

  • 服务号