Elemene inhibits the migration and invasion of 4T1 murine breast cancer cells via heparanase

Elemene inhibits the migration and invasion of 4T1 murine breast cancer cells via heparanase
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榄香烯通过乙酰肝素酶抑制4T1小鼠乳腺癌细胞的迁移和侵袭

DOI:
10.3892/mmr.2017.6638
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发表时间:
2017-05
影响因子:
3.4
通讯作者:
Zhang Gan-Lin
Zhang Gan-Lin
中科院分区:
医学4区
文献类型:
--
作者:
Zhang Yi;Sun Xu;Nan Nan;Cao Ke-Xin;Ma Cong;Yang Guo-Wang;Yu Ming-Wei;Yang Lin;Li Jin-Ping;Wang Xiao-Min;Zhang Gan-Lin

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榄香烯(ELE)是一种从姜黄中提取的天然植物药物,在中国被广泛用于癌症治疗已有20多年的历史。尽管据报道它是一种广谱抗癌药物,但其在治疗乳腺癌中的作用机制仍有待充分阐明。肝素酶是一种哺乳动物内切- d -葡萄糖醛酸苷酶,参与细胞外基质(ECM)的降解,从而促进肿瘤的进展和转移。下调肝素酶可有效减少肿瘤的恶性行为。在本研究中,使用Cell Counting kit 8测定法评估了ELE在乳腺癌细胞中的抑制作用。采用伤口愈合实验、实时细胞分析和Transwell实验来研究癌细胞的迁移和侵袭能力。此外,western blot分析用于评估关键蛋白表达水平的变化。本研究以低分子肝素(LMWH)为阳性对照,证实了ELE的抗增殖和抗转移作用。此外,ELE还下调了肝素酶的表达,降低了细胞外信号调节激酶和AKT的磷酸化。这些发现提示ELE可能是一种靶向肝素酶治疗乳腺癌的有前景的药物。
Elemene (ELE), a natural plant drug extracted from Curcumae Rhizoma, has been widely used for cancer treatment in China for more than 20 years. Although it is reported to be a broad-spectrum anticancer drug, the mechanism underlying the action of ELE in the treatment of breast cancer remains to be fully elucidated. Heparanase, a mammalian endo-D-glucuronidase, is involved in degradation of the extracellular matrix (ECM), and thus promotes tumor progression and metastasis. The downregulation of heparanase can effectively reduce tumor malignant behaviors. In the present study, the inhibitory effects of ELE were evaluated in breast cancer cells using a Cell Counting kit 8 assay. The migratory and invasive capabilities of cancer cells were investigated using a wound healing assay, real-time cell analysis and a Transwell assay. In addition, western blot analysis was used to assess alterations in the expression levels of key proteins. The present results confirmed the antiproliferative and antimetastatic effects of ELE, using low-molecular weight heparin (LMWH) as a positive control. In addition, ELE was demonstrated to downregulate the expression of heparanase, and decrease the phosphorylation of extracellular signal-regulated kinase and AKT. These findings suggested that ELE may be a promising agent targeting heparanase in the treatment of breast cancer.
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