在乳腺癌中,SB218078抑制血管生成和上皮-介质酶转变
Qianxue Wu1, Jiawei Xu2, Xin Tang3
1Department of Hepatobiliary Surgery, The First Affiliated Hospital of Chongqing Medical University, Chongqing, China.
Frontiers in pharmacology
|March 31, 2025
概括
SB218078通过抑制Chk1/ZEB1轴对乳腺癌的瘤血管生成和上皮-介质细胞转变 (EMT) 进行双重向. 这种新的方法提供了一个有前途的治疗策略,与VEGFR2抑制剂相比,副作用减少.
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:
- 血管内皮生长因子受体2 (VEGFR2) 抑制剂因副作用而面临临临床挑战.
- 瘤血管生成和上皮-介质细胞过渡 (EMT) 是乳腺癌进展中的关键过程.
- 需要新的治疗策略,同时针对血管生成和EMT.
研究的目的:
- 评估新型化合物SB218078作为针对乳腺癌血管生成和EMT的双重向剂.
- 阐明SB218078的作用机制,重点关注Chk1/ZEB1信号通路.
主要方法:
- 在体外测试中评估了SB218078对内皮细胞的抗血管性作用.
- 在体内研究中使用斑马鱼血管生成模型和小鼠异种移植来研究乳腺癌的进展.
- 机理学研究涉及基因干预的Chk1/ZEB1信号轴.
主要成果:
- SB218078抑制了体外和体内血管生成,并降低了乳腺癌细胞的攻击性和瘤生长.
- 通过Chk1的抑制,SB218078通过选择性抑制ZEB1,一个关键的EMT转录因子.
- ZEB1的淘汰效应模仿了SB218078的抗血管效应,而ZEB1的过度表达则逆转了这些效应.
结论:
- SB218078通过阻断乳腺癌中的血管生成和EMT,证明了双重作用的治疗潜力.
- Chk1-ZEB1轴是SB218078双重活动的关键机制.
- SB218078是一个有前途的新型策略,与传统的VEGFR2抑制剂不同,需要进一步的临床前开发.
相关概念视频
Regulation of Angiogenesis and Blood Supply
2.5K
Rapidly dividing tumors, embryos, and wounded tissues require more oxygen than usual, lowering the oxygen concentration in the blood. At low oxygen or hypoxic conditions, an oxygen-sensitive transcription factor called the hypoxia-inducible factor 1 or HIF1 is activated. HIF1 is a dimeric protein of alpha (ɑ) and beta (β) subunits. Under optimal oxygen conditions, HIF1β is present in the nucleus while HIF1ɑ remains in the cytosol. HIF1ɑ is hydroxylated by prolyl...
2.5K
Mitogens and the Cell Cycle
6.3K
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...
6.3K
Inhibition of Cdk Activity
4.6K
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...
4.6K
The Retinoblastoma Gene
4.0K
Tumor suppressor genes are normal genes that can slow down cell division, repair DNA mistakes, or program the cells for apoptosis in case of irreparable damage. Hence, they play an essential role in preventing the proliferation of damaged cells.
The first-ever tumor suppressor gene called Rb was identified in retinoblastoma - a rare eye tumor in children. In inherited forms of the disease, a child inherits one defective copy of the Rb gene, which predisposes them to retinoblastoma. However,...
The first-ever tumor suppressor gene called Rb was identified in retinoblastoma - a rare eye tumor in children. In inherited forms of the disease, a child inherits one defective copy of the Rb gene, which predisposes them to retinoblastoma. However,...
4.0K
Metastasis
5.5K
Metastasis is the spread of cancer cells from the original site to distant locations in the body. Cancer cells can spread via blood vessels (hematogenous) as well as lymph vessels in the body.
Epithelial-to-Mesenchymal Transition
The epithelial-to-mesenchymal transition or EMT is a developmental process commonly observed in wound healing, embryogenesis, and cancer metastasis. EMT is induced by transforming growth factor-beta (TGF-β) or receptor tyrosine kinase (RTK) ligands, which further...
Epithelial-to-Mesenchymal Transition
The epithelial-to-mesenchymal transition or EMT is a developmental process commonly observed in wound healing, embryogenesis, and cancer metastasis. EMT is induced by transforming growth factor-beta (TGF-β) or receptor tyrosine kinase (RTK) ligands, which further...
5.5K


