一种经过修改的天然小分子通过与Tubb3相互作用来抑制三阴性乳腺癌的生长
Hongwei Han1, Minkai Yang1, Zhongling Wen1
1State Key Laboratory of Pharmaceutical Biotechnology, Institute of Plant Molecular Biology, School of Life Sciences, Nanjing University, Nanjing, 210023, China; Co-Innovation Center for Sustainable Forestry in Southern China, MOE Key Laboratory of Forest Genetics and Biotechnology, Nanjing Forestry University, Nanjing, 210037, China.
概括
一种新型的什科宁衍生物PMMB276有效向三阴性乳腺癌 (TNBC) 的β-图林同型III (Tubb3). 这种Tubb3抑制剂抑制瘤生长,为TNBC治疗提供了一个有前途的新治疗途径.
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:
- 三阴性乳腺癌 (TNBC) 缺乏向治疗,预后不佳,需要新的治疗策略.
- 贝塔图林同型III (Tubb3) 与癌症进展有关,是TNBC的潜在治疗标.
- 石康宁是一种天然化合物,表现出抗瘤活性,通过结构修饰有可能提高疗效.
研究的目的:
- 为了研究一种新型什科宁衍生物PMMB276.6的抗TNBC作用,PMMB276.
- 为了阐明PMMB276在TNBC中的潜在作用机制.
主要方法:
- 对什科宁类型的查,以确定PMMB276.6.
- 使用流细胞计,免疫光,免疫阻塞,免疫沉和siRNA沉默用于体外分析.
- 采用 iTRAQ 蛋白质组学用于目标识别和 in vivo 小鼠模型进行疗效评估.
主要成果:
- PMMB276通过抑制增殖,诱导亡,并导致G2/M细胞周期停止,显示出显著的抗TNBC活性.
- Tubb3被确定为PMMB276的分子标,该化合物调节微管体动态.
- 在体内研究证实,PMMB276,通过抑制Tubb3,减少了乳腺癌的小鼠模型中的瘤生长.
结论:
- 作为Tubb3抑制剂,PMMB276在治疗三阴性乳腺癌方面表现出治疗潜力.
- 这些发现为开发希科宁衍生物作为抗TNBC剂提供了基础.
相关概念视频
Drugs that Stabilize Microtubules
2.0K
Microtubules are dynamic structures that undergo cycles of catastrophe and rescue. The microtubules play a central role in cell division by forming the spindle apparatus for segregating the chromosomes. This makes them ideal targets for regulating dividing cells in tumors and malignant cancer cells. Microtubule stabilizing drugs help stabilize the microtubule formation and promote its polymerization. Paclitaxel was the first microtubule stabilizing agent used as anticancer drug in chemotherapy...
2.0K
Drugs that Destabilize Microtubules
2.0K
Microtubules are dynamic structures and can be regulated by microtubule targeting agents (MTAs). Microtubule destabilizing drugs are a class of MTAs that destabilize and prevent microtubules' polymerization. Both natural and synthetic chemicals can be found under this class of drugs. Vincristine and vinblastine, two vinca alkaloids, and colchicine were among the first to be discovered. These drugs can affect cells in various ways, either by inducing a change in cell morphology, preventing...
2.0K
Targeted Cancer Therapies
7.6K
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...
7.6K
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
Inhibition of Cdk Activity
4.8K
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...
4.8K
TGF - β Signaling Pathway
7.4K
The TGF-β signaling pathway regulates cell growth, differentiation, adhesion, motility, and development. TGF-β ligands that induce TGF-β signaling are synthesized in their latent form. Several proteases or cell surface receptors such as integrins act upon the latent form, releasing the active ligand. There are three types of mammalian TGF-βs: (TGF-β1, TGF-β2, and TGF-β3) that bind as homodimers or heterodimers to TGF-β receptors. The TGF-β receptors...
7.4K


