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龙牙草甲醇提取物对 HT1080 细胞基质金属蛋白酶的抑制作用。

The inhibitory effect of Agrimonia Pilosa methanolic extract on matrix metalloproteinases in HT1080 cells.

机构信息

Department of Applied Chemistry & Food Engineering, Dong-Eui University, Busan, Republic of Korea.

Department of Applied Chemistry, Dong-Eui University, Busan, Republic of Korea.

出版信息

J Food Biochem. 2021 Sep;45(9):e13894. doi: 10.1111/jfbc.13894. Epub 2021 Aug 10.

Abstract

The risk of cancer increases with aging due to the accumulation of cellular deterioration that can spread to other organs through the blood and lymphatic vessels. Therefore, the inhibition of metastasis is a major concern for the treatment of cancer. Several synthetic drugs have been developed for the treatment of various cancers. However, these drugs are effective; nonspecific action and side effects on the normal human cells limit their wide acceptance, thus demanding some potential alternative. Hence, the present study emphasizes investigating the effect of a methanolic extract of Agrimonia Pilosa (APLME) on matrix metalloproteinases (MMPs) in human fibroblast sarcoma cells. The action of APLME on MMP-2 and MMP-9 was investigated using gelatin zymography. APLME suppressed the activities of MMP-2 and MMP-9 in PMA (phorbol myristate acetate)-treated HT1080 cells. In addition, western blot analysis and immunofluorescence were performed to investigate the effect of APLME on the expression of the proteins that are the major proteins involved in cell invasion and metastasis. APLME treatment inhibited the expression of MMP-2 and MMP-9 in addition to the activations of JNK, ERK, and AKT-1. Furthermore, APLME was observed to suppress cell invasion related to metastasis using cell invasion assay. Therefore, the above findings indicate that APLME inhibits the expression activity of MMP-2 and MMP-9 via inactivation of ERK and JNK in addition to AKT-1, leading to inhibiting cell invasion. Therefore, these results indicate that APLME may be used as a candidate substance for inhibiting cell invasion. PRACTICAL APPLICATIONS: Cancer increases the cell invasion to other organs through the blood and lymphatic vessels. Cancer cells deplete the nutrients and create new blood vessels that infiltrate and metastasize to other tissues. Therefore, this present study examined the effect of Agrimonia Pilosa on cell invasion. It was found that Agrimonia Pilosa methanolic extract inhibited the invasion of cancer cells through the inactivation of ERK and JNK. In addition, APLME reduced the activation and protein expression of MMP-2 and MMP-9 in addition to AKT-1. Thus, APLME can be utilized as a potential alternative therapeutic agent for inhibiting metastasis.

摘要

由于细胞恶化的积累,癌症风险会随着年龄的增长而增加,这种恶化可能通过血液和淋巴管扩散到其他器官。因此,抑制转移是癌症治疗的主要关注点。已经开发了几种合成药物来治疗各种癌症。然而,这些药物虽然有效,但对正常人体细胞的非特异性作用和副作用限制了它们的广泛接受程度,因此需要一些潜在的替代药物。因此,本研究强调了研究一种龙牙草甲醇提取物(APLME)对人成纤维肉瘤细胞基质金属蛋白酶(MMPs)的影响。使用明胶酶谱法研究了 APLME 对 MMP-2 和 MMP-9 的作用。APLME 抑制 PMA(十四烷酰佛波醇乙酸酯)处理的 HT1080 细胞中 MMP-2 和 MMP-9 的活性。此外,进行了 Western blot 分析和免疫荧光分析,以研究 APLME 对参与细胞侵袭和转移的主要蛋白质表达的影响。APLME 处理抑制了 MMP-2 和 MMP-9 的表达以及 JNK、ERK 和 AKT-1 的激活。此外,用细胞侵袭实验观察到 APLME 抑制与转移相关的细胞侵袭。因此,上述发现表明,APLME 通过灭活 ERK 和 JNK 以及 AKT-1 抑制 MMP-2 和 MMP-9 的表达活性,从而抑制细胞侵袭。因此,这些结果表明 APLME 可能被用作抑制细胞侵袭的候选物质。 实际应用:癌症通过血液和淋巴管将细胞侵袭到其他器官。癌细胞消耗营养物质并产生新的血管,这些血管渗透并转移到其他组织。因此,本研究检查了龙牙草对细胞侵袭的影响。结果发现,龙牙草甲醇提取物通过灭活 ERK 和 JNK 抑制癌细胞的侵袭。此外,APLME 降低了 MMP-2 和 MMP-9 的激活和蛋白表达以及 AKT-1。因此,APLME 可作为抑制转移的潜在替代治疗剂。

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