B4通过通过内在亡抑制纤维细胞生长因子结合蛋白1来抑制淋巴瘤的进展
Krishnapriya M Varier1,2, Gou Dan1, Xiaolong Li1
1School of Pharmaceutical Sciences, Guizhou Medical University, Guiyang, China.
Frontiers in pharmacology
|July 15, 2024
概括
一种新型的黄胺,B4,通过向FGFBP1,一种促进癌症进展的蛋白质,有效地抑制淋巴瘤的生长. 这种化合物诱导细胞亡和细胞循环停止,为淋巴瘤治疗提供了一个有前途的新途径.
科学领域:
- 在瘤学瘤学.
- 分子生物学分子生物学
- 药理学 药理学是指药理学的学科.
背景情况:
- 淋巴瘤是一个重大的全球健康问题,在全球排名第五的最常见的癌症.
- 用小分子向特定的细胞蛋白质是淋巴瘤治疗的有希望的策略.
- FGFBP1 (纤维细胞生长因子结合蛋白1) 涉及癌症进展,并且在各种癌症中被上调,使其成为潜在的治疗点.
研究的目的:
- 为了研究从Cajanus cajan中分离的黄蛋白B4的潜力,作为用于淋巴瘤治疗的FGFBP1抑制剂.
- 阐明B4影响淋巴瘤细胞生长和进展的机制.
- 在临床前淋巴瘤模型中评估B4的疗效.
主要方法:
- 使用淋巴瘤细胞系进行体外研究,以评估B4对细胞增殖,细胞亡和细胞周期的影响.
- RNA测序分析以确定由B4调节的基因及其对FGFBP1表达的影响.
- 使用淋巴瘤小鼠模型进行体内研究,以评估B4对生存率的影响.
- 药物亲和度响应目标稳定性 (DARTS) 测试以确认B4与FGFBP1.1的结合.
- 用患者衍生的原发性淋巴瘤细胞进行实验,以评估B4的疗效.
主要成果:
- 黄B4通过诱导酶依赖的内在亡和G1/S阶段细胞周期停止,选择性地抑制了淋巴瘤细胞生长.
- RNA测序证实B4抑制FGFBP1,调节参与B细胞增殖和DNA复制的基因.
- 在淋巴瘤小鼠模型中,B4显著增加了生存率.
- B4通过FGFBP1下调证明了通过FGFBP1下调来强烈抑制患者衍生的原发性淋巴瘤细胞.
- DARTS实验证实了B4与FGFBP1的强烈结合,而FGFBP1的过度表达增强了B4的敏感性.
结论:
- 黄B4作为一种新的和选择性的FGFBP1抑制剂,用于淋巴瘤治疗.
- B4的机制包括降低FGFBP1的调节,诱导内在亡,导致线粒体和DNA损伤,并阻止细胞循环.
- 这些发现支持B4作为淋巴瘤的潜在治疗剂,强调其在临床前模型和患者衍生细胞中的有效性.
关键词:
FGFBP1FGFBP1FGFBP1FGFBP1FGFBP1FGFBP1FGFBP1FGFBP1FGFBP1FGFBP1FGFBP1FGFBP1FGFBP1在FGF信号传输.灭症 (apoptosis) 是一种死亡的过程.这种类型的黄类药物是flavonoid.抑制剂抑制剂的使用淋巴瘤淋巴瘤是什么更多相关视频
08:02Isolation of Primary Cancer-Associated Fibroblasts from a Syngeneic Murine Model of Breast Cancer for the Study of Targeted Nanoparticles
Published on: May 14, 2021
5.6K
06:00Through the Looking Glass: Time-lapse Microscopy and Longitudinal Tracking of Single Cells to Study Anti-cancer Therapeutics
Published on: May 14, 2016
11.0K
相关概念视频
The 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
Inhibition of Cdk Activity
4.7K
The orderly progression of the cell cycle depends on the activation of Cdk protein by binding to its cyclin partner. However, the cell cycle must be restricted when undergoing abnormal changes. Most cancers correlate to the deregulated cell cycle, and since Cdks are a central component of the cell cycle, Cdk inhibitors are extensively studied to develop anticancer agents. For instance, cyclin D associates with several Cdks, such as Cdk 4/6, to form an active complex. The cyclin D-Cdk4/6 complex...
4.7K
Abnormal 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
The Extrinsic Apoptotic Pathway
6.3K
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...
6.3K
Targeted Cancer Therapies
7.5K
The targeted cancer therapies, also known as “molecular targeted therapies,” take advantage of the molecular and genetic differences between the cancer cells and the normal cells. It needs a thorough understanding of the cancer cells to develop drugs that can target specific molecular aspects that drive the growth, progression, and spread of cancer cells without affecting the growth and survival of other normal cells in the body.
There are several types of targeted therapies against...
There are several types of targeted therapies against...
7.5K
TGF - β Signaling Pathway
7.3K
The TGF-β signaling pathway regulates cell growth, differentiation, adhesion, motility, and development. TGF-β ligands that induce TGF-β signaling are synthesized in their latent form. Several proteases or cell surface receptors such as integrins act upon the latent form, releasing the active ligand. There are three types of mammalian TGF-βs: (TGF-β1, TGF-β2, and TGF-β3) that bind as homodimers or heterodimers to TGF-β receptors. The TGF-β receptors...
7.3K
