School of Pharmacy, Health Science Center, Xi'an Jiaotong University No. 76, Yanta Weststreet, #54, Xi'an, Shaanxi Province, P.R. China.
Am J Transl Res. 2015 Jan 15;7(1):39-52. eCollection 2015.
Centipede Scolopendra, a commonly used traditional Chinese medicine, has been shown to have anti-cancer effects. In this study, the inhibitory effect of alcohol extracts of Centipede Scolopendra (AECS) was more prominent when treating cells highly expressing epidermal growth factor receptor (EGFR) (A431 and HEK293/EGFR cells versus HEK293 cells). The elution profiles of AECS on cell membrane chromatography (CMC) column showed that AECS could bind to EGFR, and competition studies indicated that AECS and gefitinib may have direct competition at a single common binding site on EGFR. SiRNA knockdown of EGFR in A431 cells attenuated AECS effects, suggesting that EGFR was a target mediated by AECS. In a cell culture system, AECS dramatically induced apoptosis of A431 and HEK293/EGFR cells, which was associated with the effects on Bcl-2 family. Furthermore, AECS could alter EGFR kinase activity and reduce phosphorylation of EGFR and downstream signaling players AKT and Erk1/2. The mechanism of AECS to inhibit high-EGFR expression cell proliferation is due to its ability to induce apoptosis and modulate the EGFR pathway. This study might provide a novel therapy for cancer with high-EGFR expression.
蜈蚣是一种常用的中药，已被证明具有抗癌作用。在这项研究中，蜈蚣醇提物（AECS）对高表达表皮生长因子受体（EGFR）的细胞（A431 和 HEK293/EGFR 细胞与 HEK293 细胞相比）的抑制作用更为明显。AECS 在细胞膜色谱（CMC）柱上的洗脱图谱表明，AECS 可以与 EGFR 结合，竞争研究表明，AECS 和吉非替尼可能在 EGFR 上的单个共同结合位点具有直接竞争。A431 细胞中 EGFR 的 siRNA 敲低减弱了 AECS 的作用，表明 EGFR 是 AECS 介导的靶标。在细胞培养系统中，AECS 可显著诱导 A431 和 HEK293/EGFR 细胞凋亡，这与 Bcl-2 家族的作用有关。此外，AECS 可以改变 EGFR 激酶活性，降低 EGFR 及其下游信号分子 AKT 和 Erk1/2 的磷酸化。AECS 抑制高 EGFR 表达细胞增殖的机制是由于其诱导细胞凋亡和调节 EGFR 途径的能力。这项研究可能为高 EGFR 表达的癌症提供一种新的治疗方法。
