由亡细胞分泌的精子胺通过调节骨髓瘤中β-catenin活性来增强化疗耐药性
概括
精子胺 (SPD) 通过增强癌症干和药物流动来增加骨髓瘤的化学抵抗. 使用DFMO抑制SPD合成可以提高化疗的有效性,为骨髓瘤治疗提供了一种新的治疗策略.
科学领域:
- 在瘤学瘤学.
- 分子生物学分子生物学
- 生物化学 生物化学
背景情况:
- 化学抵抗是骨髓瘤 (OS) 治疗的一个主要挑战.
- 了解化学抵抗的机制对于开发有效疗法至关重要.
研究的目的:
- 调查精素 (SPD) 在骨髓瘤中介化疗抵抗的作用.
- 阐明SPD影响OS化学抵抗的潜在分子机制.
主要方法:
- 使用了骨髓瘤细胞系和异种移植.
- 采用了包括流细胞测量,西式涂抹,蛋白质质量谱和RNA测序在内的技术.
- 评估了药理学SPD合成抑制 (DFMO) 对体外和体内抗化学剂的影响.
主要成果:
- 在OS细胞中,化疗诱导的亡会导致精子胺 (SPD) 合成的增加.
- 发现SPD可以降低OS细胞中西斯丁 (CDP) 和多克索鲁比辛 (DOX) 的疗效.
- SPD增强β-catenin活性,促进癌症干和ABC转运体表达,促进药物耐药性.
- 使用DFMO抑制SPD合成显著改善了OS细胞对CDP和DOX的化学敏感性.
结论:
- 由亡细胞产生的代谢物,如SPD,在治疗耐药性中起着至关重要的作用.
- 向SPD生物合成是一种潜在的治疗策略,可以提高骨髓瘤化疗的疗效.
更多相关视频
相关概念视频
Treatment Resistant Cancers
3.7K
Cancer is the second leading cause of death in the United States. A cancer cell is genetically unstable and hence can mutate faster. They can also modify their microenvironment and escape immune surveillance. The difficulties in treating cancer are further compounded by the emergence of rapid resistance to anticancer drugs. The most common ways to attain resistance in cancer cells include alteration in drug transport and metabolism, modification of drug target, elevated DNA damage response, or...
3.7K
Abnormal Proliferation
5.1K
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...
5.1K
Metastasis
6.3K
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...
6.3K
Inhibition of Cdk Activity
5.5K
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...
5.5K
Targeted Cancer Therapies
8.6K
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...
8.6K


