针对ClpP的ONC206诱导线粒体功能障碍和肝细胞癌细胞的保护性自
Jiahao Cao1, Fei Cao2, Chuanzheng Wang2
1Xiamen Key Laboratory of Translational Medical of Digestive System Tumor, Fujian Provincial Key Laboratory of Chronic Liver Disease and Hepatocellular Carcinoma, Zhongshan Hospital of Xiamen University, School of Medicine, Xiamen University, Xiamen, 361004, PR China; Department of Thyroid Head and Neck Surgery, The Second Affiliated Hospital of Jiaxing University, Jiaxing, 314099, PR China.
一种强效药物模拟物ONC206,通过诱导亡和线粒体功能障碍,有效抑制肝细胞癌 (HCC) 的生长. 它还触发保护性自,可以阻断以增强其在肝癌中的抗癌作用.
科学领域:
- 在瘤学瘤学.
- 分子生物学分子生物学
- 药物发现 药物发现 药物发现
背景情况:
- 肝细胞癌 (HCC) 是最常见的肝癌形式.
- 在其他癌症中,ONC201显示出治疗的前景;其类似的ONC206在HCC中的作用尚未被探索.
研究的目的:
- 阐明ONC206在肝细胞癌 (HCC) 的作用机制.
- 研究ONC206对HCC细胞增殖,细胞亡,自和线粒体功能的影响.
主要方法:
- 细胞增殖试验的测定.
- 细胞亡测定试验
- 线粒体功能的分析 (MMP,ROS)
- 自的评估 自的评估
- 对于ClpPP的西部涂抹
- ClpP的击倒实验进行了试验.
主要成果:
- ONC206抑制了HCC细胞的增殖,并诱导了细胞亡.
- ONC206触发了细胞保护性自,而阻断自则增强了它的亲细胞灭绝效应.
- ONC206导致线粒体功能障碍,包括胀,减少MMP和增加ROS积累.
- 在HCC样本中的ClpP水平升高调解了ONC206的作用;ClpP的降低逆转了ONC206的细胞毒性.
结论:
- 通过诱导亡和线粒体功能障碍,ONC206表现出抗HCC活性.
- ONC206通过ClpP激活HCC细胞中的保护性自.
- ClpP是ONC206在肝细胞癌中的抗癌作用的关键调解剂.
更多相关视频
13:20Detection of Mitochondria Membrane Potential to Study CLIC4 Knockdown-induced HN4 Cell Apoptosis In Vitro
Published on: July 17, 2018
19:44Enhancement of Apoptotic and Autophagic Induction by a Novel Synthetic C-1 Analogue of 7-deoxypancratistatin in Human Breast Adenocarcinoma and Neuroblastoma Cells with Tamoxifen
Published on: May 30, 2012
相关概念视频
Electron Transport Chain: Complex I and II
ROS generation is regulated and maintained at moderate levels necessary...
Targeted Cancer Therapies
There are several types of targeted therapies against...
Autophagic Cell Death
Autophagy and Apoptosis
Autophagy can activate apoptosis. In normal conditions, the autophagy activating protein Beclin-1 and...
The Intrinsic Apoptotic Pathway
Combination Therapies and Personalized Medicine
The combination of the drug acetazolamide and sulforaphane is a good example of combination therapy to treat cancer. The cells in the interior of a large tumor often die due to the hypoxic and...
Cancer Therapies
However, cancer treatments can pose several challenges, as therapies used to kill cancer cells are generally also toxic to normal cells. Moreover, cancer cells mutate rapidly and can develop resistance to chemical agents or radiation therapy. Besides, all types of cancer cells may not respond to the same therapy. Some cancer cells respond to one...
