昂科纳斯通过调节ROS恒温,抗氧化蛋白表达和线粒体动力学来诱导Dabrafenib耐药黑色素瘤细胞系的亡
Carlotta Passarini1, Alessia Cardile1, Filippo Zuanetti1
1Biological Chemistry Section, Department of Neuroscience, Biomedicine and Movement Science, University of Verona, Strada Le Grazie, 8, I-37134 Verona, Italy.
International journal of molecular sciences
|February 27, 2026
概括
瘤酶 (ONC) 通过破坏它们的氧化还原平衡和线粒体功能,有效地准黑色素瘤细胞. 这种两动物核糖核酶在抗药性黑色素瘤方面表现特别有前途.
科学领域:
- 生物化学 生物化学
- 分子生物学分子生物学
- 在瘤学瘤学.
背景情况:
- 晚期黑色素瘤由于耐药性而难以治疗.
- 形酶 (ONC),一种两动物核糖酶,表现出选择性的黑色素瘤细胞细胞毒性.
- 了解ONC在抗药性黑色素瘤中的机制至关重要.
研究的目的:
- 在BRAF突变黑色素瘤细胞中研究ONC的分子机制.
- 分析ONC对氧化应激,线粒体动态和细胞死亡的影响.
- 确定ONC在对dabrafenib敏感和耐药黑色素瘤的疗效.
主要方法:
- 评估反应性氧物种 (ROS) 水平和NRF2通路.
- 评估了线粒体生物发生,裂变和线粒体衰变的标志物 (PGC1α,DRP1,FIS1,PINK1).
- 分析了细胞灭绝 (caspase-9),自 (beclin1,ATG3,LC3B),脂质过氧化和扩散途径 (STAT3,NF-κB).
主要成果:
- ONC增加了ROS和降低了NRF2依赖的抗氧化剂,特别是在耐药细胞中.
- ONC抑制了线粒体生物发生和裂变,导致线粒体扩大.
- 通过caspase-9激活,ONC损害了线粒/自和诱导了亡,同时降低了生存率.
- ONC抑制了STAT3,NF-κB和循环素依赖的激酶,并诱导了脂质过氧化.
结论:
- 在黑色素瘤中,ONC破坏了氧化还原稳定,线粒体功能和生存信号.
- ONC表现出强大的抗黑色素瘤活性,特别是在BRAF抑制剂耐药人群中.
- ONC要求进一步研究作为抗药性黑色素瘤的治疗剂.
关键词:
DRP1 DRP1 的使用方法FSP1SP1 在线播放总的来说,GCLM是一个很好的公司.这就是HO-1的HO-1.在OPA1中,OPA1是OPA1.标签:PINK1PINK1PINK1PINK1PINK1在 SLC7A1111 中.这就是SOD2的原因.c-Myccc 的意思是我的幸存者 幸存者 幸存者更多相关视频
06:09Spatial and Temporal Control of Murine Melanoma Initiation from Mutant Melanocyte Stem Cells
Published on: June 7, 2019
9.6K
09:32Drug-Induced Senescence in Liver Cells Promotes M2 Macrophage Polarization: Implications for Tyrosine Kinase Inhibitor-Associated Hepatotoxicity
Published on: October 17, 2025
582
相关概念视频
01:31The Intrinsic Apoptotic Pathway
8.9K
Internal cellular stress, such as cellular injury or hypoxia, triggers intrinsic apoptosis. The B-cell lymphoma 2 (Bcl-2) family of proteins are the primary regulators of the intrinsic apoptotic pathway. For example, during DNA damage, checkpoint proteins, such as Ataxia Telangiectasia Mutated (ATM protein) and Checkpoints Factor-2 (Chk2) proteins, are activated. These proteins phosphorylate p53 which further activates pro-apoptotic proteins, such as Bax, Bak, PUMA, and Noxa, and inhibits...
8.9K
02:50Combination Therapies and Personalized Medicine
6.2K
Combining two or more treatment methods increases the life span of cancer patients while reducing damage to vital organs or tissue from the overuse of a single treatment. Combination therapy also targets different cancer-inducing pathways, thus reducing the chances of developing resistance to treatment.
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...
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...
6.2K
01:17The Extrinsic Apoptotic Pathway
9.0K
The extrinsic apoptotic pathway is initiated when extracellular death-inducing signals, such as specific cytokines, activate the death receptors expressed on the cell surface. The immune cells involved in this pathway are natural killer cells (NK cells) and cytotoxic T-lymphocytes. NK cells are critical in innate immune response, while cytotoxic T-lymphocytes are associated with adaptive immune response. These cells recognize specific receptors expressed on the altered cells and activate...
9.0K
01:46Electron Transport Chain: Complex I and II
19.2K
The mitochondrial electron transport chain (ETC) is the main energy generation system in the eukaryotic cells. However, mitochondria also produce cytotoxic reactive oxygen species (ROS) due to the large electron flow during oxidative phosphorylation. While Complex I is one of the primary sources of superoxide radicals, ROS production by Complex II is uncommon and may only be observed in cancer cells with mutated complexes.
ROS generation is regulated and maintained at moderate levels necessary...
ROS generation is regulated and maintained at moderate levels necessary...
19.2K
01:24Caspases
14.4K
Caspase, a family of cysteine proteases, serve as effectors in apoptosis. The ced3 gene in C.elegans was first identified to be involved in apoptosis. This gene encodes the ced-3 caspase that is similar to the interleukin-1-beta converting enzyme or ICE in mammals. In addition to apoptosis, caspases also function in the inflammatory response. Inflammatory caspases are essential in activating pro-inflammatory cytokines that recruit immune cells and block the replication of pathogens inside...
14.4K
01:30Apoptosis
16.2K
Apoptosis is a combination of two Greek words, 'apo' and 'ptosis,' meaning separation and falling off, respectively. Hippocrates used this word to describe gangrene, which was caused due to bandaging of fractured bones. Apoptosis was distinguished from necrosis in 1970 when John Kerr reported observations of morphological changes occurring during apoptosis. During one experiment, he observed that the disruption of blood supply to the liver tissue resulted in a size...
16.2K