阻断C5a/C5aR通路促进了CuS介导的癌症治疗效果,通过抑制cuproptosis耐药性
Hong Yang1, Boshao Deng1, Xiao Han1
1Department of Immunology, Army Medical University, Chongqing, China.
Journal for immunotherapy of cancer
|June 8, 2025
概括
这项研究揭示了C5a/C5aR通路驱动癌症中cuproptosis抵抗. 将硫化铜纳米颗粒与C5a受体对抗剂结合起来,可以克服这种抗性,增强抗瘤效应,改善癌症治疗.
科学领域:
- 在瘤学瘤学.
- 免疫学 免疫学 免疫学
- 纳米医学是一种纳米医学.
背景情况:
- 乳腺癌是全球主要的恶性瘤,铜亡 (铜诱导的细胞死亡) 成为瘤进展和治疗反应的关键因素.
- 抗cuproptosis是癌症治疗中的一个重大挑战,需要对其潜在机制进行更深入的研究.
- 铜纳米颗粒显示出作为治疗剂的希望,但克服耐药性对于有效性至关重要.
研究的目的:
- 为了研究C5a/C5aR通路在乳腺癌中介于cuproptosis耐药性的作用.
- 评估将硫化铜 (CuS) 纳米颗粒与C5a受体对抗剂 (C5aRA) 结合起来,以克服cuproptosis耐药性和增强抗瘤效应的潜力.
主要方法:
- 利用单细胞RNA测序,生物信息学,生存分析和免疫组织化学来分析C5a/C5aR通路和乳腺癌中的cuproptosis.
- 通过体外和体内实验评估CuS纳米粒子和C5aRA的抗瘤作用,包括细胞活力,增殖,活性氧物种水平和异种移植小鼠模型.
- 使用ELISA研究了CuS纳米颗粒激活补充系统.
主要成果:
- 发现C5a/C5aR通路通过Wnt/β-catenin通路通过上调ATP7B表达来促进cuproptosis耐药性.
- 使用CuS纳米颗粒,激光治疗和C5aRA的组合疗法通过克服cuproptosis耐药性,显著提高了抗瘤疗效.
- 观察到协同效应的治疗效应,整合了针对性治疗,免疫疗法和光热疗法.
结论:
- 这项研究为癌细胞中C5a/C5aR通路介导的型亡耐药性提供了第一个证据.
- 将CuS纳米颗粒与C5aRA结合,为提高癌症治疗结果提供了一种新且卓越的治疗策略.
更多相关视频
13:38Synthesis and Characterization of an Aspirin-fumarate Prodrug that Inhibits NFκB Activity and Breast Cancer Stem Cells
Published on: January 18, 2017
12.2K
06:54Evaluation of the Interplay Between the Complement Protein C1q and Hyaluronic Acid in Promoting Cell Adhesion
Published on: June 15, 2019
6.0K
相关概念视频
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
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
The Intrinsic Apoptotic Pathway
6.4K
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...
6.4K
Anaphase Promoting Complex
2.8K
The stepwise destruction of specific proteins is necessary for the progression and completion of the cell cycle. Such proteins are ubiquitinated by ubiquitin ligases and then subsequently destroyed by the proteasome. The SCF (Skp1/Cullin/F-box) and the anaphase-promoting complex (APC) are two important ubiquitin ligases involved in cell cycle progression. While SCF is active throughout the cell cycle, APC gets activated during metaphase to anaphase transition. Cdc20 or Cdh1 binds to APC and...
2.8K
Tumor Immunotherapy
493
Immunotherapy is a treatment that boosts or manipulates the immune system to fight diseases, including cancer. For instance, by stimulating an immune response through vaccinations against viruses that cause cancers, like hepatitis B virus and human papillomavirus, these diseases can be prevented. Nonetheless, some cancer cells can avoid the immune system due to their rapid mutation and division. The immune response to many cancers involves three phases: elimination, equilibrium, and escape.
493
Drugs that Stabilize Microtubules
2.0K
Microtubules are dynamic structures that undergo cycles of catastrophe and rescue. The microtubules play a central role in cell division by forming the spindle apparatus for segregating the chromosomes. This makes them ideal targets for regulating dividing cells in tumors and malignant cancer cells. Microtubule stabilizing drugs help stabilize the microtubule formation and promote its polymerization. Paclitaxel was the first microtubule stabilizing agent used as anticancer drug in chemotherapy...
2.0K
