血管生成
癌症研究
上皮-间质转换
生物
转移
细胞生长
小干扰RNA
A549电池
基因沉默
血管内皮生长因子
细胞培养
细胞
化学
分子生物学
癌症
生物化学
转染
血管内皮生长因子受体
基因
遗传学
作者
Mingqi Wang,Jiaqing Yan,Xinyu Cao,Peiyan Hua,Zhengqiang Li
标识
DOI:10.1016/j.bcp.2019.113775
摘要
Hydrogen sulfide (H2S) has been frequently implicated in tumor progression. However, the exact regulation mechanism of H2S in human non-small cell lung cancer (NSCLC) has not been fully elucidated. Here, analysis of NSCLC biopsies and adjacent non-tumor tissues revealed selectively high levels of endogenous H2S-producing enzymes, cystathionine-beta-synthase (CBS), cystathionine-gamma-lyase (CSE) and 3-mercaptopyruvate sulfurtransferase (MPST). Similarly, quantitative real-time PCR (qRT-PCR) and western blot results showed that NSCLC cell lines (A549, 95D) expressed higher levels of CBS, CSE and MPST in mRNA and enzyme proteins, respectively. Moreover, NSCLC cell lines produced more H2S than did the normal lung epithelial cell line BEAS-2B. H2S was further detected to induce NSCLC migration and invasion, as well as the epithelial mesenchymal transition (EMT) process. Small interfering RNA (siRNA) silencing of CBS or CSE activity reduced proliferation and metastasis potential of tumor cells. In addition, H2S modulated hypoxia-inducible factor-1α (HIF-1α) to stimulate vascular endothelial growth factor (VEGF) expression, which contributes to tumor angiogenesis. Treatment of nude mice with pharmacological inhibition of CBS or CSE activity decreased xenograft growth and suppressed angiogenesis. Collectively, these results indicate H2S plays an important part in NSCLC growth and angiogenesis by HIF-1α activation, which potentially provide new insight in therapeutic strategies.
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