通过激活NF-κB2/BCL3通路,LTBP2通过激活GC细胞中的西斯普拉丁耐药性来调节
Jun Wang1, Wenjia Liang2, Xiangwen Wang1
1The First Hospital of Lanzhou University, Department of General Surgery, Ward 6, Lanzhou, Gansu, China.
Genetics and molecular biology
|April 5, 2024
概括
沉默潜伏转化生长因子β结合蛋白2 (LTBP2) 通过抑制NF-κB2通路,提高了胃癌中西斯的敏感性. 这表明LTBP2是克服耐药性的潜在治疗标.
科学领域:
- 在瘤学瘤学.
- 分子生物学分子生物学
背景情况:
- 胃癌 (GC) 经常会对西斯普拉丁化疗产生耐药性.
- 潜伏转化生长因子β结合蛋白2 (LTBP2) 与GC有关,但其在西斯抗药性中的作用尚不清楚.
研究的目的:
- 调查LTBP2在胃癌中对西斯普拉丁耐药性的作用.
- 阐明LTBP2对化学抵抗的影响背后的分子机制.
主要方法:
- 在GC细胞系中评估LTBP2表达.
- 进行了细胞活力测试,以将LTBP2表达与西斯普拉丁敏感性相关联.
- 利用晶状病毒介导的LTBP2沉默和GC细胞中的基因过度表达.
- 分析了NF-κB2/Bcl-3/cyclin D1信号通路.
主要成果:
- 在HGC-27细胞中抑制LTBP2增强了思丁的敏感性,减少了增殖,并抑制了NF-κB2/Bcl-3/cyclin D1通路.
- 在LTBP2沉默细胞中过度表达NFκB2,恢复了对西斯的敏感性,并上调了p52/Bcl-3/cyclin D1.
- 沉默LTBP2有效抑制细胞增殖和减轻西斯普拉丁耐药性.
结论:
- 通过向非正规的NF-κB2 p52/Bcl-3/cyclin D1通路,LTBP2沉默克服了胃癌中西斯普拉丁耐药性的作用.
- 在胃癌患者中,LTBP2代表了一种有前途的治疗点,可以提高思丁的疗效.
相关概念视频
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
02:26NF-κB-dependent Signaling Pathway
7.4K
The transcription factor NF-κB was discovered in 1986 in the lab of Nobel laureate Professor David Baltimore, for its interaction with the immunoglobulin light chain enhancer in B-cells. After more than three decades of study, it is now evident that NF-κB regulates the expression of over 100 genes. Most of these genes play an essential role in the innate and adaptive immune responses as well as the inflammatory responses of animals.
NF-κB-dependent Signaling Mechanism
The...
NF-κB-dependent Signaling Mechanism
The...
7.4K
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
01:23Negative 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
02:37DNA Damage can Stall the Cell Cycle
9.1K
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...
9.1K