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山茱萸粗提物通过丝裂原活化蛋白激酶信号通路抑制基质金属蛋白酶-2/-9,从而抑制U-2 OS人骨肉瘤细胞的迁移和侵袭。

The crude extract of Corni Fructus inhibits the migration and invasion of U-2 OS human osteosarcoma cells through the inhibition of matrix metalloproteinase-2/-9 by MAPK signaling.

作者信息

Liao Ching-Lung, Lin Ju-Hwa, Lien Jin-Cherng, Hsu Shu-Chun, Chueh Fu-Shin, Yu Chien-Chih, Wu Ping-Ping, Huang Yi-Ping, Lin Jaung-Geng, Chung Jing-Gung

机构信息

Graduate Institute of Chinese Medicine, China Medical University, Taichung, 404, Taiwan.

出版信息

Environ Toxicol. 2015 Jan;30(1):53-63. doi: 10.1002/tox.21894. Epub 2013 Aug 19.

Abstract

Osteosarcoma is the most common primary malignancy of the bone cancers. In the Chinese population, the crude extract of Corni Fructus (CECF) has been used as Traditional Chinese medicine to treat several different diseases for hundreds of years. In the present study, effects of CECF on inhibition of migration and invasion in U-2 OS human osteosarcoma cells were examined. CECF significantly inhibited migration and invasion of U-2 OS human osteosarcoma cells. We also found that CECF inhibited activities of matrix metalloproteinases-2 (MMP-2) and matrix metalloproteinases-9 (MMP-9). CECF decreased protein levels of FAK, PKC, SOS1, MKK7, MEKK3, GRB2, NF-κB p65, COX-2, HIF-1α, PI3K, Rho A, ROCK-1, IRE-1α, p-JNK1/2, p-ERK1/2, p-p38, Ras, p-PERK, MMP-2, MMP-9, and VEGF in U-2 OS cells. Results of this study indicate that CECF may have potential as a novel anticancer agent for the treatment of osteosarcoma by inhibiting migration and invasion of cancer cells.

摘要

骨肉瘤是骨癌中最常见的原发性恶性肿瘤。在中国人群中,山茱萸粗提取物(CECF)作为中药用于治疗多种不同疾病已有数百年历史。在本研究中,检测了CECF对人骨肉瘤U-2 OS细胞迁移和侵袭的抑制作用。CECF显著抑制了人骨肉瘤U-2 OS细胞的迁移和侵袭。我们还发现CECF抑制了基质金属蛋白酶-2(MMP-2)和基质金属蛋白酶-9(MMP-9)的活性。CECF降低了U-2 OS细胞中FAK、PKC、SOS1、MKK7、MEKK3、GRB2、NF-κB p65、COX-2、HIF-1α、PI3K、Rho A、ROCK-1、IRE-1α、p-JNK1/2、p-ERK1/2、p-p38、Ras、p-PERK、MMP-2、MMP-9和VEGF的蛋白水平。本研究结果表明,CECF可能通过抑制癌细胞的迁移和侵袭,具有作为治疗骨肉瘤的新型抗癌药物的潜力。

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