β2-AR抑制增强了EGFR抗体的有效性,阻碍了氧化应激反应机制
Vitale Del Vecchio1, Luigi Mele1, Sameer Kumar Panda1
1Department of Experimental Medicine, University of Campania "Luigi Vanvitelli", Naples, Italy.
Cell death & disease
|September 18, 2023
概括
使用ICI和Cetuximab (CTX) 阻止β2-上腺素受体 (β2-AR) 有效地抑制了头癌的生长. 在临床前模型中,这种组合疗法通过向瘤性途径和抗氧化剂反应来减少瘤的进展.
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:
- β2-上腺素受体 (β2-ARs) 是参与应激反应的GPCRs.
- 在各种癌症中,β2-AR信号促进瘤的发展,转变和治疗抵抗.
- 在头部和部状细胞癌 (HNSCC) 中,β2-AR抑制通过调节p38/NF-kB和NRF-2通路来增强MEK 1/2细胞毒性.
研究的目的:
- 为了验证β2-AR阻断的抗瘤作用.
- 研究β2-AR阻断与MEK/ERK和EGFR通路抑制的协同效应.
- 评估这些组合疗法在临床前正型HNSCC小鼠模型中.
主要方法:
- 使用了HNSCC.的临床前正位体小鼠模型.
- 使用β2-AR抑制剂 (ICI) 和EGFR mAb Cetuximab (CTX) 联合使用.
- 评估了β2-AR表达,瘤生长,MAPK信号传递 (MEK/ERK酸化) 和NRF-2介导的抗氧化反应.
主要成果:
- 在HNSCC瘤中观察到显著的β2-AR表达.
- 联合ICI和CTX治疗显著降低了瘤生长和β2-AR表达.
- 治疗诱导了MAPK信号通路的关闭,并阻止了NRF-2核转位,破坏了ROS恒温.
结论:
- β2-AR抑制在治疗HNSCC.中表现出有效性.
- 在临床前的HNSCC模型中,ICI和Cetuximab的联合治疗显示出显著的抗瘤作用.
- 这种组合为无法切除的HNSCC提供了一个有希望的治疗策略,可能是通过向关键的瘤和抗氧化途径.
更多相关视频
05:21Author Spotlight: Optimizing Antibody-Based Cancer Treatments via Antibody-Dependent, Cell-Mediated Cytotoxicity Assay
Published on: September 13, 2024
395
08:15Author Spotlight: Network Pharmacology and Molecular Docking to Decipher the Action of Jiawei Shengjiang San Against Diabetic Kidney Disease
Published on: May 10, 2024
610
相关概念视频
01:17Antihypertensive Drugs: Action of β1 Blockers
476
β1-receptors are primarily located in the heart and kidneys. In cardiac myocytes, these receptors interact with neurotransmitters released by the sympathetic nervous system during heightened activity or danger. As a result, β1-receptors get activated, initiating a series of biochemical processes. Excessive activation of beta receptors due to chronic stress can abnormally increase heart rate and contractility, resulting in high blood pressure or hypertension. To counteract this,...
476
01:27Adrenergic Antagonists: Pharmacological Actions of β-Receptor Blockers
886
β-receptor blockers significantly impact the cardiovascular system by counteracting catecholamine-induced sympathetic responses. These medications decrease heart rate, contractility, and cardiac output, potentially leading to cardiac depression, life-threatening bradycardia, and death. Therapeutically, β-blockers function as mild antihypertensives and are utilized in treating angina pectoris and cardiac arrhythmias. However, nonselective β-blockers inhibit β2-receptors in...
886
01:28Antihypertensive Drugs: Types of β-Blockers
732
β receptors are classified into three subclasses: β1, β2, and β3. β1 receptors are primarily located in the heart and kidneys. When they get activated, they increase heart rate, contractility, and renin release. This process enhances blood pressure and aids in stress management. In contrast, β2 receptors are situated mainly in the lungs, blood vessels, and skeletal muscles. Upon activation, they trigger smooth muscle relaxation, causing bronchodilation and...
732
02:38Mitogens and the Cell Cycle
6.5K
Mitogens and their receptors play a crucial role in controlling the progression of the cell cycle. However, the loss of mitogenic control over cell division leads to tumor formation. Therefore, mitogens and mitogen receptors play an important role in cancer research. For instance, the epidermal growth factor (EGF) - a type of mitogen and its transmembrane receptor (EGFR), decides the fate of the cell's proliferation. When EGF binds to EGFR, a member of the ErbB family of tyrosine kinase...
6.5K
01:31Adrenergic Antagonists: ɑ and β-Receptor Blockers
511
Third-generation β-blockers, such as labetalol and carvedilol, represent a significant advancement in managing cardiovascular conditions. Unlike conventional β-blockers, which can induce peripheral vasoconstriction, third-generation drugs block α1 adrenoceptors. This promotes vasodilation through several mechanisms, such as increased nitric oxide production, inhibition of calcium ion entry, opening of potassium ion channels, and antioxidant action. Labetalol, for instance, is...
511
01:30Antihypertensive Drugs: Angiotensin II Receptor Blockers
776
In the renin-angiotensin-aldosterone system, a hormone called angiotensin II plays a crucial role. It binds to the AT1 receptors in vascular smooth muscles coupled with Gq proteins. The activation of these receptors activates an enzyme called phospholipase C, which releases two molecules: inositol trisphosphate and diacylglycerol. These molecules cause a chain reaction that leads to the phosphorylation of myosin light chains and promotes interaction between actin and myosin, leading to smooth...
776