荷莫哈林顿因通过调节HIF-1α/ERβ/E2F1前循环促进非小细胞肺癌细胞死亡
Qi Su1, Jiayan Ren1, Kun Chen1
1School of Pharmacy, Health Science Center, Xi'an Jiaotong University, No. 76, Yanta West Street, #54, Xi'an, Shaanxi 710061, China.
The Journal of pharmacy and pharmacology
|September 11, 2024
概括
荷莫哈林顿因 (HHT) 通过破坏HIF-1α/ERβ/E2F1信号通路来抑制非小细胞肺癌 (NSCLC) 的生长. 这项研究揭示了HHTHT.
科学领域:
- 在瘤学瘤学.
- 分子生物学分子生物学
- 癌症研究 癌症研究
背景情况:
- 低氧诱导因素 (HIF) 驱动非小细胞肺癌 (NSCLC) 的进展.
- HIF-1α可能调节雌激素受体β (ERβ),影响NSCLC的生长.
- 植物化学物质同素 (HHT) 对NSCLC表现出抑制作用,但其在缺氧下的机制尚不清楚.
研究的目的:
- 研究HIF-1α/ERβ/E2F1信号在NSCLC进展中的作用.
- 阐明同素 (HHT) 在低氧条件下抑制NSCLC生长的分子机制.
- 探索HHT在NSCLC中的治疗潜力.
主要方法:
- 细胞活力,殖民地形成和流动细胞计测试被用来评估HHT对NSCLC的影响.
- 西方涂抹,分子对接,位点定向突变发生,免疫组织化学和免疫光被用来探索机制.
- 使用H460异种移植模型来评估HHT在体内的疗效.
主要成果:
- 一个HIF-1α/ERβ/E2F1前循环促进NSCLC的生长,并与生存率低下有关.
- HHT通过ubiquitin-proteasome路径抑制这种循环,抑制HIF-1α和ERβ蛋白表达.
- HHT与ERβ的GLU305位点结合,抑制增殖,殖民地形成,并在NSCLC细胞和异种移植中促进细胞亡.
结论:
- HIF-1α/ERβ/E2F1前循环是NSCLC生长的一个关键驱动力.
- 通过向这种途径,HHT有效地抑制NSCLC.
- 这项研究揭示了NSCLC中HT诱导的细胞死亡的新机制.
相关概念视频
02:39lncRNA - Long Non-coding RNAs
8.5K
In humans, more than 80% of the genome gets transcribed. However, only around 2% of the genome codes for proteins. The remaining part produces non-coding RNAs which includes ribosomal RNAs, transfer RNAs, telomerase RNAs, and regulatory RNAs, among other types. A large number of regulatory non-coding RNAs have been classified into two groups depending upon their length – small non-coding RNAs, such as microRNA, which are less than 200 nucleotides in length, and long non-coding RNA...
8.5K
02:53Adaptive Mechanisms in Cancer Cells
5.7K
Cancer cells accumulate genetic changes at an abnormally rapid rate due to the defects in the DNA repair mechanisms. From an evolutionary perspective, such genetic instability is advantageous for cancer development. Mutant cell lines accumulate a series of beneficial mutations that contribute to their progression into cancer.
Some of the advantages that cancer cells have on normal cells include - enhanced ability to divide without terminally differentiating, induce new blood vessel formation,...
Some of the advantages that cancer cells have on normal cells include - enhanced ability to divide without terminally differentiating, induce new blood vessel formation,...
5.7K
01:24Regulation of Angiogenesis and Blood Supply
2.5K
Rapidly dividing tumors, embryos, and wounded tissues require more oxygen than usual, lowering the oxygen concentration in the blood. At low oxygen or hypoxic conditions, an oxygen-sensitive transcription factor called the hypoxia-inducible factor 1 or HIF1 is activated. HIF1 is a dimeric protein of alpha (ɑ) and beta (β) subunits. Under optimal oxygen conditions, HIF1β is present in the nucleus while HIF1ɑ remains in the cytosol. HIF1ɑ is hydroxylated by prolyl...
2.5K
03:03mTOR 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
02:38Mitogens and the Cell Cycle
6.4K
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...
6.4K