Department of Thoracic Surgery, The Second Hospital of Tianjin Medical University, Tianjin, China.
Department of Neurology, Tianjin Medical University General Hospital, Tianjin, China.
Thorac Cancer. 2019 Jan;10(1):90-95. doi: 10.1111/1759-7714.12905. Epub 2018 Nov 28.
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.
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.
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.
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.
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。
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。
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。
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。