Tumor-derived exosomes, which contain RNA, DNA, and proteins, have been a potentially rich non-invasive source of bi-omarkers. However, no efficient isolation or detection methods are yet available. Here, we developed...

The present study aimed to provide data to support the association between cystathionine-γ-lyase (CSE) and breast cancer metastasis. Reverse transcription-quantitative polymerase chain reaction, immunohistochemistry and western blot analysis were used to detect the mRNA and protein expression levels of CSE in human breast cancer tissues and cells. MTS and 5-ethynyl-2′-deoxyuridine assays were used to assess cell viability and proliferation. Scratch wound and Transwell assays were conducted to determine cell migration and invasion. In addition, hydrogen sulfide determination was performed using the methylene blue method. The expression of CSE was upregulated in samples from patients with breast cancer that also exhibit lymph node metastasis, and in grade III and readily metastatic breast cancer cell lines. The proliferation, migration and invasion of breast cancer cells were examined in the present study, and tumor metastasis was observed in nude mice. The function of CSE in breast cancer metastasis depends on the vascular endothelial growth factor (VEGF) signaling pathway, a key mediator of angiogenesis that is crucial for the development and metastasis of tumors. CSE positively regulated the expression of VEGF and increased the levels of certain key proteins in the VEGF pathway, including the phosphoinositide (PI3K)/protein kinase B (AKT) pathway [PI3K, Akt and phosphorylated (p)Akt], focal adhesion kinase (FAK)-paxillin pathway (FAK and paxillin) and rat sarcoma (Ras)-mitogen-activated protein kinase pathway [Ras, rapidly accelerated fibrosarcoma, extracellular signal-regulated kinase (ERK)1/2 and pERK1/2]. Furthermore, the novel CSE inhibitor I157172 possessed antiproliferative and anti-metastatic activities in early MDA-MB-231 metastatic breast cancer cells via inhibition of the VEGF signaling pathway, which further confirmed the role of CSE in breast cancer metastasis. Overall, these data demonstrate for the first time, to the best of our knowledge, that the functions of CSE in breast cancer metastasis are associated with the VEGF signaling pathway.

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Cystathionine γ-lyase (CSE) is highly expressed in breast cancer, and can promote breast cancer development and progression; therefore, inhibitors of CSE may be of great significance for the treatment of breast cancer. The present study identified the CSE inhibitor I157172 through virtual screening and confirmed its activity. Subsequently, the effects and mechanism of I157172 on breast cancer cells were investigated. MTS and 5-ethynyl-2'-deoxyuridine (EdU) assays were used to assess cell viability and proliferation. Scratch wound and Transwell assays were conducted to determine cell migration and invasion. In addition, H 2 S determination was performed using the methylene blue method, and western blotting was performed to detect protein expression. The results revealed that I157172 significantly inhibited the growth, proliferation and migration of MCF7 breast cancer cells in a dose-dependent manner. The results of further mechanistic studies demonstrated that CSE expression was negatively associated with sirtuin 1 (SIRT1) in human breast cancer tissues and cells, and CSE knockdown resulted in an increase in SIRT1 expression, and a decrease in acetylated (acetyl)signal transducer and activator of transcription 3 (STAT3) and phosphorylated (p)-STAT3 levels in MCF7 cells. Furthermore, STAT3 downstream proteins B-cell lymphoma 2, p-protein kinase B, matrix metalloproteinase (MMP)-2 and MMP-9 were inhibited in CSE knockdown MCF7 cells. In addition, I157172 induced upregulation of SIRT1, and downregulation of acetyl-STAT3 and p-STAT3 (Tyr705), as well as inhibition of STAT3 downstream proteins. Taken together, I157172 inhibited the growth, proliferation and migration of breast cancer cells via upregulating SIRT1, which consequently mediated deacetylation of STAT3 and inactivation of the STAT3 pathway.

Nanoparticle (NP) surfaces are modified immediately by the adsorption of proteins when injected into human blood, leading to the formation of a protein corona. The protein‐coated NPs may be recognized by living cells. Furthermore, the adsorption of serum proteins is a continuous competitive dynamic process that is the key to exploring the bioapplication and biosafety of NPs. In this study, the competitive dynamic adsorption of some serum proteins on gold nanoparticles (AuNPs) is investigated by fluorescence emission, dynamic light scattering, and sodium dodecyl sulfate‐polyacrylamide gel electrophoresis. Serum proteins with different AuNPs binding affinities are used to address the competitive dynamic process of protein‐AuNP interactions in vitro. The results show that more abundant serum proteins, such as human serum albumin, adsorb on AuNPs first, and then the higher binding affinity and lower concentration serum proteins, such as fibrinogen (FIB), replace the abundant and lower binding affinity serum proteins. However, the lower binding affinity serum proteins, such as hemoglobin, do not replace the higher binding affinity proteins from the protein‐AuNP conjugates. During the dynamic exchange process, the larger the binding affinities difference between two proteins, the faster the exchange rate. This dynamic exchange process usually takes longer in inner protein‐AuNP conjugates (hard corona) than the external surface of protein‐AuNP conjugates (soft corona).

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