相关实验视频

Updated: Jun 29, 2025

Evaluating the Effectiveness of Cancer Drug Sensitization In Vitro and In Vivo

Evaluating the Effectiveness of Cancer Drug Sensitization In Vitro and In Vivo

Published on: February 6, 2015

西斯普拉丁通过抑制胆管癌中的ZEB1/Nfe2l1来破坏蛋白质体反弹效应

Yuancai Xiang^1,2, Man Jia², Yuan Gao¹

¹Department of Pathophysiology, College of High Altitude Military Medicine, Third Military Medical University (Army Medical University), 400038 Chongqing, China.

Frontiers in bioscience (Landmark edition)

|March 27, 2024

概括

西斯普拉丁通过抑制ZEB1/Nfe2l1通路来克服胆管癌中的博特佐米布耐药性,该通路抑制了蛋白质酶体反弹. 这一发现为用蛋白酶体抑制剂治疗固体瘤提供了新的策略.

科学领域:

在瘤学瘤学.
分子生物学分子生物学
药物耐药性药物耐药性药物耐药性

背景情况:

博特佐米布 (BTZ) 对血液性恶性瘤有效,但由于药物耐药性,对胆管癌等固体瘤的疗效有限.
抵抗的一个关键机制是蛋白酶体反弹效应,在最初的抑制后,蛋白酶体活动会反弹,但基本机制尚未完全理解.
了解蛋白酶抑制剂如何诱导这种效应对于开发更有效的癌症疗法至关重要.

研究的目的:

研究胆管癌中博特佐米布耐药性的机制,特别是蛋白酶体反弹效应.
为了确定分子目标和途径参与调解这种抵抗.
评估涉及博尔特佐米布和西斯普拉丁的组合疗法的潜力.

主要方法:

胆管癌细胞被用博特佐米布 (Bortezomib,BTZ),西斯丁或两者一起治疗.
基因和蛋白质表达水平Nfe2l1和蛋白质组子单元使用qPCR和西部涂抹分析.
转录组测序发现ZEB1是Nfe2l1的调节者;ZEB1敲击和记者分析证实了它在调节蛋白质组基因和活性方面的作用.

主要成果:

西斯普拉丁治疗通过降低Nfe2l1水平,抑制了BTZ治疗细胞中的蛋白酶子单元基因表达和活性.
ZEB1被确定为Nfe2l1的上游转录因子,对蛋白酶体基因表达和活性至关重要.
抑制ZEB1抑制了蛋白酶体活性,并与BTZ和西斯普拉丁相结合,显著降低了胆管癌细胞活力.

结论:

西斯丁通过抑制ZEB1/Nfe2l1轴来破坏BTZ诱导的蛋白酶体反弹效应在胆管癌中.
这项研究揭示了一种新的机制,该机制是对蛋白酶体抑制剂耐药性的基础.
这些发现为开发结合蛋白酶体抑制剂与向ZEB1/Nfe2l1通路的药物用于胆管癌和其他固体瘤的新疗法提供了理由.

关键词:

现在我们有了Nfe2l1l1 在ZEB1中,ZEB1是指ZEB1.博尔特佐米布 (Bortezomib) 是一种药物.胆瘤是一种胆瘤.西斯普拉丁 (cisplatin) 是一种制剂.

更多相关视频

Author Spotlight: Exploring the Role of FAM83A in Cervical Cancer

Author Spotlight: Exploring the Role of FAM83A in Cervical Cancer

Published on: February 9, 2024

Acute Kidney Injury Model Induced by Cisplatin in Adult Zebrafish

Acute Kidney Injury Model Induced by Cisplatin in Adult Zebrafish

Published on: May 15, 2021

相关概念视频

Abnormal Proliferation

Abnormal Proliferation

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...

Negative Regulator Molecules

Negative Regulator Molecules

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.

Induced Pluripotent Stem Cells

Induced Pluripotent Stem Cells

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...

Targeted Cancer Therapies

Targeted Cancer Therapies

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...

DNA Damage can Stall the Cell Cycle

DNA Damage can Stall the Cell Cycle

In response to DNA damage, cells can pause the cell cycle to assess and repair the breaks. However, the cell must check the DNA at certain critical stages during the cell cycle. If the cell cycle pauses before DNA replication, the cells will contain twice the amount of DNA. On the other hand, if cells arrest after DNA replication but before mitosis, they will contain four times the normal amount of DNA. With a host of specialized proteins at their disposal,cells must use the right protein at...

Inhibition of Cdk Activity

Inhibition of Cdk Activity

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...