库尔库抑制血管造型模仿通过调节细胞癌中的ETS-1
Yue Chong1,2,3, Shan Xu1,2,3, Tianjie Liu1,2,3
1Department of Urology, The First Affiliated Hospital of Xi'an Jiaotong University, Xi'an, 710061, China.
Current cancer drug targets
|February 1, 2024
概括
库尔库明通过向血管生成模仿 (VM) 来抑制细胞癌 (RCC) 的进展. 这种天然化合物通过降低ETS-1,VE-Cadherin和MMP9的调节来抑制瘤细胞形成的血液供应,提供了一个潜在的治疗策略.
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:
- 转移性细胞癌 (RCC) 是一个重大的临床挑战,尤其是在对向治疗产生耐药性时.
- 血管仿真 (VM) 是一种由瘤驱动的血管化过程,使得癌细胞能够绕过常规治疗.
- 天然化合物黄素对RCC中VM的治疗潜力在很大程度上仍未被探索.
研究的目的:
- 调查黄素在细胞癌中调节VM形成中的作用和分子机制.
- 确定参与黄素在RCC中的抗VM作用的关键分子标.
主要方法:
- 利用RNA测序,免疫阻塞和免疫组织化学来分析RCC细胞和组织中的基因和蛋白质表达 (ETS-1,VE-Cadherin,MMP9).
- 采用等离子体转染物对ETS-1的淘汰和过度表达,以评估其在VM中的作用.
- 通过体外管形成试验和体内动物实验量化VM形成,使用CD31-PAS双染色进行通道识别.
主要成果:
- 在临床样本中,VM形成与RCC等级和阶段正相关.
- 黄素在体外证明了对VM形成的剂量和时间依赖的抑制.
- RNA测序发现ETS-1是VM的关键调节者;它的调节影响了VE-Cadherin和MMP9的表达以及随后的VM.
- 黄素通过抑制ETS-1,VE-Cadherin和MMP9表达在体外和体内都抑制了VM.
结论:
- 黄素通过降低ETS-1,VE-Cadherin和MMP9的表达,抑制RCC中的VM.
- 这些发现表明黄素是抑制VM和控制RCC进展的潜在治疗剂.
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