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重组人源化内皮抑素诱导的 HMGB1 表达抑制抑制非小细胞肺癌癌细胞的增殖。

Recombined humanized endostatin-induced suppression of HMGB1 expression inhibits proliferation of NSCLC cancer cells.

机构信息

Department of Thoracic Surgery, The Second Hospital of Tianjin Medical University, Tianjin, China.

Department of Neurology, Tianjin Medical University General Hospital, Tianjin, China.

出版信息

Thorac Cancer. 2019 Jan;10(1):90-95. doi: 10.1111/1759-7714.12905. Epub 2018 Nov 28.

Abstract

BACKGROUND

Recombined humanized endostatin (Rh-endostatin) exhibits a potent anti-cancer effect involving multiple molecular targets and signaling pathways. HMGB1 is a highly conserved DNA-binding protein involved in cancer development. The therapeutic effect of Rh-endostatin on HMGB1 has not been reported, thus we investigate the effect in non-small cell lung cancer (NSCLC) cells.

METHODS

Quantitative real-time PCR and Western blot were used to analyze the messenger RNA and protein expression of HMGB1 in A549 cancer cells, while enzyme-linked immunosorbent assay was used to detect the release of HMGB1. Western blot was performed to evaluate HMGB1 expression in SK-MES-1 and H661 NSCLC cells.

RESULTS

Rh-endostatin inhibited the proliferation of A549 cancer cells and distinctly downregulated the expression and release of HMGB1 in dose and time dependent manners. Rh-endostatin-induced HMGB1 downregulation was confirmed in different types of NSCLC cells.

CONCLUSION

These results demonstrate the general phenomenon that Rh-endostatin can induce HMGB1 suppression in a variety of NSCLC cells. Rh-endostatin may suppress HMGB1 expression and release in A549 cancer cells, thus inhibiting cell proliferation.

摘要

背景

重组人血管内皮抑制素(rh-endostatin)具有多种分子靶点和信号通路的强大抗癌作用。HMGB1 是一种高度保守的 DNA 结合蛋白,参与癌症的发生。rh-endostatin 对 HMGB1 的治疗作用尚未见报道,因此我们研究了其在非小细胞肺癌(NSCLC)细胞中的作用。

方法

采用实时定量 PCR 和 Western blot 分析 A549 癌细胞中 HMGB1 的信使 RNA 和蛋白表达,采用酶联免疫吸附试验检测 HMGB1 的释放。Western blot 检测 SK-MES-1 和 H661 NSCLC 细胞中 HMGB1 的表达。

结果

rh-endostatin 抑制 A549 癌细胞的增殖,并呈剂量和时间依赖性显著下调 HMGB1 的表达和释放。rh-endostatin 诱导的 HMGB1 下调在不同类型的 NSCLC 细胞中得到证实。

结论

这些结果表明 rh-endostatin 可诱导多种 NSCLC 细胞中 HMGB1 的普遍抑制现象。rh-endostatin 可能通过抑制 HMGB1 的表达和释放来抑制 A549 癌细胞的增殖。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8faa/6312838/2092534dd1c4/TCA-10-90-g001.jpg

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