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核糖核酸酶通过半胱天冬酶-9/-3信号通路诱导人胶质母细胞瘤DBTRG、GBM8901和GBM8401细胞系的细胞凋亡。

ribonuclease induces cell apoptosis via the caspase-9/-3 signaling pathway in human glioblastoma DBTRG, GBM8901 and GBM8401 cell lines.

作者信息

Chen Jen-Ni, Yiang Giou-Teng, Lin Yi-Fan, Chou Pei-Lun, Wu Tsai-Kun, Chang Wei-Jung, Chen Chinshuh, Yu Yung-Luen

机构信息

Department of Food Science and Biotechnology, National Chung Hsing University, Taichung 402, Taiwan, R.O.C. ; Department of Nutrition, Master Program of Biomedical Nutrition, Hungkuang University, Taichung 433, Taiwan, R.O.C.

Department of Emergency Medicine, Taipei Tzu Chi Hospital, Buddhist Tzu Chi Medical Foundation, New Taipei 231, Taiwan, R.O.C. ; Department of Emergency Medicine, School of Medicine, Tzu Chi University, Hualien 970, Taiwan, R.O.C.

出版信息

Oncol Lett. 2015 Jun;9(6):2471-2476. doi: 10.3892/ol.2015.3117. Epub 2015 Apr 15.

Abstract

Human glioblastoma multiforme is one of the most aggressive malignant brain tumor types, and the mean survival time of patients with a brain tumor is <2 years when traditional therapies are administered. Thus, numerous studies have focused on the development of novel treatments for brain tumors. Frog ribonucleases, such as Onconase and ribonuclease (RC-RNase), exert antitumor effects on various tumor cells, including cervical cancer, breast cancer, hepatoma, leukemia, pancreatic cancer and prostate cancer cells. In addition, frog Onconase has been applied as a treatment in clinical trials. However, the antitumor effects of frog ribonucleases on brain tumors are unclear. Previous studies have indicated that RC-RNase demonstrates a decreased cytotoxic effect in normal cells compared with Onconase. Therefore, the present study investigated the ability of RC-RNase to exert antitumor activities on human glioblastoma. It was found that RC-RNase inhibits the growth of the human glioblastoma DBTRG, GBM8901 and GBM8401 cells. In addition, the present study revealed that RC-RNase induces caspase-9/-3 activity and triggers the apoptotic cell death pathway in human glioblastoma cells. Notably, it was also demonstrated that RC-RNase effectively inhibits the growth of human glioblastoma tumors in a nude mouse model. Overall, the present study indicates that RC-RNase may be a potential agent for the treatment of human glioblastoma.

摘要

多形性胶质母细胞瘤是最具侵袭性的恶性脑肿瘤类型之一,采用传统疗法时,脑肿瘤患者的平均生存时间小于2年。因此,众多研究聚焦于脑肿瘤新疗法的开发。青蛙核糖核酸酶,如昂卡酶和核糖核酸酶(RC-RNase),对包括子宫颈癌、乳腺癌、肝癌、白血病、胰腺癌和前列腺癌细胞在内的多种肿瘤细胞具有抗肿瘤作用。此外,青蛙昂卡酶已在临床试验中用作一种治疗方法。然而,青蛙核糖核酸酶对脑肿瘤的抗肿瘤作用尚不清楚。先前的研究表明,与昂卡酶相比,RC-RNase在正常细胞中表现出降低的细胞毒性作用。因此,本研究调查了RC-RNase对人多形性胶质母细胞瘤发挥抗肿瘤活性的能力。研究发现,RC-RNase抑制人多形性胶质母细胞瘤DBTRG、GBM8901和GBM8401细胞的生长。此外,本研究还表明,RC-RNase诱导人多形性胶质母细胞瘤细胞中的半胱天冬酶-9/-3活性并触发凋亡细胞死亡途径。值得注意的是,研究还证明,RC-RNase在裸鼠模型中有效抑制人多形性胶质母细胞瘤肿瘤的生长。总体而言,本研究表明,RC-RNase可能是治疗人多形性胶质母细胞瘤的一种潜在药物。

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