在多发性骨髓瘤中,LTe2通过抑制在Thr308和Ser473的AKT酸化来诱导细胞亡
Yuanjiao Zhang1, Jiacheng Qian2, Mingmei Jiang1
1Nanjing Hospital of Chinese Medicine and School of Medicine & Holistic Integrative Medicine, Nanjing University of Chinese Medicine, Nanjing, China.
Frontiers in oncology
|October 2, 2023
概括
一种新型的醇寡合体LTe2在体外和体内有效抑制多发性骨髓瘤 (MM) 细胞的生长. 这种化合物向AKT酸化,显示出作为MM治疗的新治疗剂的前景.
科学领域:
- 血液学 血液学 血液学
- 在瘤学瘤学.
- 药理学 药理学是指药理学的学科.
背景情况:
- 多发性骨髓瘤 (MM) 是一种异质的B细胞恶性瘤,由于耐药性,复发率高.
- 印度醇寡合物,如LTe2,表现出广泛的抗癌活性.
- 需要新的治疗策略来克服MM的耐药性.
研究的目的:
- 为了研究LTe2在多发性骨髓瘤中的抗瘤功效.
- 在MM细胞中识别LTe2的下游分子标.
- 评估LTe2作为MM治疗的潜在候选药物.
主要方法:
- 使用MTT试验和5TMM3VT小鼠模型评估的体外和体外抗瘤活性.
- 用于分析MM细胞亡的流细胞计.
- 转录组RNA-seq和分子动力学 (MD) 实验阐明了它的作用机制.
主要成果:
- 在体外和体内,LTe2显著抑制了多发性髓瘤细胞的增殖.
- 在MM细胞中LTe2诱导的亡.
- 发现LTe2可以在Thr308和Ser473位点抑制AKT酸化.
结论:
- LTe2对多发性骨髓瘤有显著的抗瘤作用.
- LTe2的机制涉及到AKT信号的抑制.
- LTe2显示出作为MM的新型治疗剂的潜力,需要进一步的临床研究.
相关概念视频
PI3K/mTOR/AKT Signaling Pathway
3.6K
The mammalian target of rapamycin (mTOR) is a serine/threonine kinase that regulates growth, proliferation, and cell survival in response to hormones, growth factors, or nutrient availability. This kinase exists in two structurally and functionally distinct forms: mTOR complex 1 (mTORC1) and mTOR complex 2 (mTORC2). The first form (mTORC1) is composed of a rapamycin-sensitive Raptor and proline-rich Akt substrate, PRAS40. In contrast, mTORC2 consists of a...
3.6K
The Intrinsic Apoptotic Pathway
6.6K
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...
6.6K
Targeted Cancer Therapies
7.7K
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...
7.7K
mTOR Signaling and Cancer Progression
3.8K
The mammalian target of rapamycin or mTOR protein was discovered in 1994 due to its direct interaction with rapamycin. The protein gets its name from a yeast homolog called TOR. The mTOR protein complex in mammalian cells plays a major role in balancing anabolic processes such as the synthesis of proteins, lipids, and nucleotides and catabolic processes, such as autophagy in response to environmental cues, such as availability of nutrients and growth factors.
The mTOR pathway or the...
The mTOR pathway or the...
3.8K
Abnormal Proliferation
4.6K
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...
4.6K
Mitogens and the Cell Cycle
6.5K
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...
6.5K


