THBS1促进血管生成,并通过HIF-1/VEGF信号通路加速ESCC恶性进展
Xiao Zhou1, Qiaoxi Xia1, Mantong Chen2
1Department of Central Laboratory, Shantou Central Hospital, Shantou, Guangdong, China.
Cell biology international
|January 18, 2024
概括
THBS1通过激活HIF-1/VEGF信号,促进食道状细胞癌 (ESCC) 的生长和血管生成,从而促进贝瓦西祖马布耐药性. 向THBS1为ESCC的抗血管生成疗法提供了一个潜在的策略.
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:
- 血栓素1 (THBS1) 表达在食道状细胞癌 (ESCC) 中升高,并与预后不佳有关.
- THBS1被认为是ESCC进展中的潜在瘤基因.
研究的目的:
- 研究THBS1在ESCC中的特定作用和分子机制.
- 探索THBS1对血管生成的影响及其对贝瓦西祖马布耐药性的潜在作用.
主要方法:
- 在ESCC细胞中抑制THBS1表达.
- 评估细胞迁移,入侵,增殖和殖民地形成.
- 评估条件介质对人类静脉内皮细胞 (HUVECs) 管形成的影响.
- 分析了HIF-1α,HIF-1β,VEGFA,CD31,p-ERK和p-AKT的蛋白质表达.
- 调查THBS1沉默和贝瓦西祖马布治疗的联合作用.
主要成果:
- 抑制THBS1抑制了ESCC细胞的迁移,入侵,增殖和殖民地形成.
- 抑制THBS1降低了HUVEC管的形成和体内血管生成 (CD31表达).
- 沉默THBS1降低了HIF-1α,HIF-1β和VEGFA蛋白的水平.
- 在HUVEC中,THBS1静音降低了p-ERK和p-AKT的激活.
- 结合THBS1沉默和贝瓦西祖马布,与单独的贝瓦西祖马布相比,显示出优异的抗血管和抗瘤作用.
结论:
- THBS1通过HIF-1/VEGF通路促进ESCC血管生成,激活HUVEC中的AKT和ERK信号.
- 在ESCC中,THBS1有助于贝瓦西祖马布耐药性.
- 在ESCC中,THBS1代表了对抗血管生成策略的有前途的治疗标.
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