伪酸B通过ROS/AMPK/mTOR/自信号通路抑制NSCLC的进展
Dan Luo1, Fang He2, Jingyun Liu2
1Faculty of Chinese Medicine, State Key Laboratory of Quality Research in Chinese Medicine, Macau University of Science and Technology, Taipa, Macao 999078, China; Department of Respiratory and Critical Care Medicine, The Affiliated Hospital of Southwest Medical University, Luzhou, Sichuan 646099, China; Inflammation & Allergic Diseases Research Unit, The Affiliated Hospital of Southwest Medical University, Luzhou, Sichuan 646099, China.
概括
伪酸B (PAB) 通过通过ROS激活的AMPK/mTOR通路诱导亡和自细胞死亡,对非小细胞肺癌 (NSCLC) 治疗具有前景.
科学领域:
- 在瘤学瘤学.
- 药理学 药理学是指药理学的学科.
- 分子生物学分子生物学
背景情况:
- 非小细胞肺癌 (NSCLC) 仍然是全球癌症相关死亡的主要原因.
- 伪酸B (PAB),来自Pseudolarix kaempferi,表现出已知的抗瘤特性.
- 了解PAB在NSCLC中的精确机制对于治疗开发至关重要.
研究的目的:
- 研究PAB对NSCLC细胞的抗癌作用 (H1975和H1650).
- 阐明潜在的分子机制,包括亡,自和信号通路.
- 在体内验证PAB的疗效.
主要方法:
- 进行了细胞活力测试,殖民地形成测试,细胞周期分析,划伤愈合测试和亡测试.
- 自标志物 (LC3 II,SQSTM1/P62) 和信号通路 (AMPK/mTOR) 通过西式斑点分析.
- 测量了反应性氧物种 (ROS) 的水平.
- 在体内研究中使用了携带NSCLC瘤的无血性裸体小鼠.
主要成果:
- PAB显著降低了NSCLC细胞活力,殖民地形成和迁移,同时诱导细胞周期停止和细胞亡.
- PAB促进了自,证实LC3 II增加和SQSTM1/P62减少,并抑制了mTOR通路,同时激活AMPK.
- PAB治疗增加了细胞内ROS水平,这与观察到的自和亡有关.
- 在体内实验证实了PAB的抗瘤活性.
结论:
- 在NSCLC中,PAB会诱导细胞亡和自细胞死亡.
- 该机制涉及ROS生成,导致AMPK/mTOR路径调节.
- PAB显示出作为NSCLC治疗剂的显著潜力.
相关概念视频
03:03mTOR Signaling and Cancer Progression
3.8K
The mammalian target of rapamycin or mTOR protein was discovered in 1994 due to its direct interaction with rapamycin. The protein gets its name from a yeast homolog called TOR. The mTOR protein complex in mammalian cells plays a major role in balancing anabolic processes such as the synthesis of proteins, lipids, and nucleotides and catabolic processes, such as autophagy in response to environmental cues, such as availability of nutrients and growth factors.
The mTOR pathway or the...
The mTOR pathway or the...
3.8K
01:22PI3K/mTOR/AKT Signaling Pathway
3.5K
The mammalian target of rapamycin (mTOR) is a serine/threonine kinase that regulates growth, proliferation, and cell survival in response to hormones, growth factors, or nutrient availability. This kinase exists in two structurally and functionally distinct forms: mTOR complex 1 (mTORC1) and mTOR complex 2 (mTORC2). The first form (mTORC1) is composed of a rapamycin-sensitive Raptor and proline-rich Akt substrate, PRAS40. In contrast, mTORC2 consists of a...
3.5K
02:23Abnormal Proliferation
4.5K
Under normal conditions, most adult cells remain in a non-proliferative state unless stimulated by internal or external factors to replace lost cells. Abnormal cell proliferation is a condition in which the cell's growth exceeds and is uncoordinated with normal cells. In such situations, cell division persists in the same excessive manner even after cessation of the stimuli, leading to persistent tumors. The tumor arises from the damaged cells that replicate to pass the damage to the...
4.5K
01:31The Intrinsic Apoptotic Pathway
6.5K
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...
6.5K
01:19Interactions Between Signaling Pathways
6.3K
Signaling cascades usually lack linearity. Multiple pathways interact and regulate one another, allowing cells to integrate and respond to diverse environmental stimuli.
Convergence and divergence, and cross-talk between signaling pathways
Two distinct signaling pathways can converge on a single functional unit, which may either be a single protein or a complex of proteins. The response is either functionally distinct or synergistic between the two pathways but different from the response...
Convergence and divergence, and cross-talk between signaling pathways
Two distinct signaling pathways can converge on a single functional unit, which may either be a single protein or a complex of proteins. The response is either functionally distinct or synergistic between the two pathways but different from the response...
6.3K
01:20The JAK-STAT Signaling Pathway
8.8K
Several cytokine receptors have tightly bound Janus kinase or JAK proteins attached at their cytosolic tail. Small signaling molecules such as cytokines, growth hormones, or prolactins bind to the cytokine receptors and initiate their dimerization. The dimerization brings the cytosolic JAKs together that trans-phosphorylate and activates each other. The activated JAKs now phosphorylate cytosolic tails of the cytokine receptors, which serve as binding sites for adaptor proteins such as SH2...
8.8K