巴巴奥丹通过抑制YAP1克服了胆管癌中西斯普拉丁耐药性
Jiong Li1, Xiangjun Ma1, Faying Xu2
1Department of Traditional Chinese Medicine, The First People's Hospital of Lin'an District, Hangzhou, China.
Pharmaceutical biology
|April 4, 2024
概括
巴巴多丹 (BBD) 与西斯普拉丁结合克服了胆管癌细胞 (CCA) 中的西斯普拉丁耐药性. BBD减少IC50,增强细胞亡和DNA损伤,并调节关键蛋白质表达,提供了一个新的治疗策略.
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:
- 胆管癌 (CCA) 呈现出侵略性行为和多药性耐药性,导致患者的预后不佳.
- 现有的治疗方法,包括西斯,由于耐药性而面临挑战.
- 巴巴多丹 (BBD) 已在非小细胞肺癌中表现出有效性,但其在CCA耐药性中的作用尚未被探索.
研究的目的:
- 调查BBD在克服胆管癌细胞 (CCA) 中的西斯普拉丁耐药性的作用和潜在机制.
- 评估BBD对CCA细胞活力,细胞亡,DNA损伤和特定分子通路的影响.
主要方法:
- 耐西斯普拉丁的CCA被用不同度的西斯普拉丁和BBD治疗.
- 评估IC50值,抑制率,细胞亡和DNA损伤,使用细胞计数套件-8,流细胞计量和彗星测定.
- 测量了谷氨 (GSH) 水平,氧化谷氨,总谷氨含量和谷氨酶活性.
主要成果:
- BBD显著降低了CCA中的西斯丁IC50,增强了抑制,亡和DNA损伤.
- BBD调节了关键蛋白质的表达,包括B细胞淋巴瘤-2,Yes相关蛋白1 (YAP1) 和ERCC切除修复1.
- BBD治疗降低了GSH水平和谷氨酸酶活性,YAP1的降低模仿了BBD的影响,YAP1的过度表达抵消了它们.
结论:
- 在胆管癌中,BBD显示出在克服西斯普拉丁耐药性的潜力.
- 该机制涉及对YAP1信号和谷氨代谢的调节.
- 这些发现为BBD在CCA治疗中的临床应用提供了科学依据.
相关概念视频
02:34Inhibition 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
02:23Abnormal 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
02:56Treatment Resistant Cancers
3.3K
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...
3.3K
01:31The 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
01:06Induced Pluripotent Stem Cells
4.1K
Stem cells are undifferentiated cells that divide and produce different cell types. Ordinarily, cells that have differentiated into a specific cell type are terminally differentiated; however, scientists have found a way to reprogram these mature cells so that they dedifferentiate and return to an unspecialized, proliferative state. These cells are pluripotent like embryonic stem cells—able to produce all cell types—and are called induced pluripotent stem cells (iPSCs).
Somatic...
Somatic...
4.1K
01:23Negative Regulator Molecules
35.4K
Positive regulators allow a cell to advance through cell cycle checkpoints. Negative regulators have an equally important role as they terminate a cell’s progression through the cell cycle—or pause it—until the cell meets specific criteria.
35.4K