首页> 外国专利> COMPOSITION FOR ENHANCING TRAIL SENSITIVITY COMPRISING INHIBITORS FOR EXPRESSION OR ACTIVITY OF TIP41 AS A TARGET GENE OF TRAIL SENSITIZER

COMPOSITION FOR ENHANCING TRAIL SENSITIVITY COMPRISING INHIBITORS FOR EXPRESSION OR ACTIVITY OF TIP41 AS A TARGET GENE OF TRAIL SENSITIZER

机译:包含TIP41的表达或活性抑制剂的作为用于增敏的靶基因的增强敏感性的组合物

摘要

The present invention relates to a pharmaceutical composition, including inhibitors for expression or activity of TIP41 protein, for prevention and treatment of cancer. When the liver cancer cell lines, showing resistance to TRAIL, are treated with TIP41 siRNA and TRAIL, apoptosis is induced in cancer cell. The same effect is found in cases of lung cancer and colon cancer with resistance against TRAIL. Moreover, this induction of apoptosis by TIP41 siRNA and TRAIL was confirmed in tumor xenograft, which was injected with Huh7 liver cancer cells and then was subjected to TIP41 siRNA transfection and TRAIL treatment. In addition, it was confirmed through animal experiments in which the tumor size has reduced and apoptosis was induced by treatment with TIP41 siRNA and TRAIL. Of note, MKK7/JNK pathway was confirmed to mediate the apoptosis induced by the application of TIP41 siRNA and TRAIL. The apoptosis were verified to be caused by the activation of MKK7/JNK signaling pathway. Taken together, the present invention provide the strong evidence that the pharmaceutical composition, including inhibitors for TIP41 expression or activity can be used for cancer prevention and treatment as well as an anti-cancer adjuvant. Taken together, the pharmaceutical composition comprising inhibitors for expression or activity of TIP41 protein may be used for prevention and treatment of cancer or as an anti-cancer adjuvant.
机译:本发明涉及用于预防和治疗癌症的药物组合物,包括用于TIP41蛋白的表达或活性的抑制剂。当用TIP41 siRNA和TRAIL处理对TRAIL具有抗性的肝癌细胞系时,会诱导癌细胞凋亡。在对TRAIL具有抗性的肺癌和结肠癌中发现了相同的效果。此外,在肿瘤异种移植物中证实了由TIP41 siRNA和TRAIL诱导的凋亡,该异种移植物中注射了Huh7肝癌细胞,然后进行了TIP41 siRNA转染和TRAIL处理。另外,通过动物实验证实了肿瘤大小减小并且通过用TIP41 siRNA和TRAIL治疗诱导了细胞凋亡。值得注意的是,证实了MKK7 / JNK途径介导了TIP41 siRNA和TRAIL的应用诱导的细胞凋亡。凋亡被证实是由MKK7 / JNK信号通路的激活引起的。综上所述,本发明提供了强有力的证据,所述药物组合物,包括用于TIP41表达或活性的抑制剂,可用于癌症的预防和治疗以及抗癌佐剂。总之,包含用于TIP41蛋白的表达或活性的抑制剂的药物组合物可用于预防和治疗癌症或用作抗癌佐剂。

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