期刊
BIOCHEMICAL PHARMACOLOGY
卷 172, 期 -, 页码 -出版社
PERGAMON-ELSEVIER SCIENCE LTD
DOI: 10.1016/j.bcp.2019.113775
关键词
Hydrogen sulfide; Non-small cell lung cancer; Hypoxia-inducible factor-1 alpha; Epithelial-mesenchymal transition; Angiogenesis
资金
- National Natural Science Foundation of China [31670797]
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-1 alpha (HIF-1 alpha) 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-1 alpha activation, which potentially provide new insight in therapeutic strategies.
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