Paris saponin VII suppresses osteosarcoma cell migration and invasion by inhibiting MMP‑2/9 production via the p38 MAPK signaling pathway.
Paris saponin VII suppresses osteosarcoma cell migration and invasion by inhibiting MMP‑2/9 production via the p38 MAPK signaling pathway.
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DOI：
10.3892/mmr.2016.5663
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发表时间：
2016-10
影响因子：
3.4
通讯作者：
Zhu Y
中科院分区：
文献类型：
--
作者：
Cheng G;Gao F;Sun X;Bi H;Zhu Y
转移是骨肉瘤死亡的主要原因。靶向转移是骨肉瘤治疗的主要策略。延龄草是一种传统中药，广泛用于治疗多种疾病，包括癌症。然而，目前尚无证据表明从延龄草中提取的巴黎皂苷VII（PS VII）对骨肉瘤细胞的抗转移作用及其机制。本研究旨在研究PS VII对骨肉瘤细胞迁移和侵袭的影响。MTT法检测骨肉瘤细胞活力和增殖能力。然后分别用划痕愈合试验和Transwell试验检测骨肉瘤细胞的迁移和侵袭。此外，基质金属蛋白酶（MMP）-2和-9的表达在mRNA和蛋白质水平测定后与PS VII的处理。用蛋白质印迹法检测丝裂原活化蛋白激酶（MAPK）的表达。最后，用p38 MAPK抑制剂验证PS VII对MMP-2和MMP-9表达以及骨肉瘤细胞迁移和侵袭的影响。这表明PS VII处理后骨肉瘤细胞的增殖、迁移和侵袭受到抑制。PS VII以剂量和时间依赖性方式下调MMP-2和MMP-9的表达。PS VII还发挥其下调p38 MAPK磷酸化的能力。此外，通过使用p38抑制剂SB 203580，揭示了PS VII在MMP-2和-9表达和骨肉瘤细胞侵袭中的作用。总之，这些结果表明PS VII通过p38 MAPK信号通路抑制骨肉瘤细胞的迁移和侵袭。
Metastasis is the primary cause of mortality in osteosarcoma. Targeting metastasis is a major strategy in osteosarcoma treatment. As a traditional Chinese medicine, Trillium tschonoskii Maxim has been widely used in the therapy of various diseases, including cancer. However, currently there is no evidence regarding the anti-metastasic effect of Paris saponin VII (PS VII), which is extracted from Trillium tschonoskii Maxim, on osteosarcoma cells and its underling mechanisms. The present study aimed to examine the effect of PS VII on the migration and invasion of osteosarcoma cells. Viability and proliferation of osteosarcoma cells were examined by MTT assay. Migration and invasion of osteosarcoma cells was then detected using scratch wound healing assays and Transwell assays, respectively. Additionally, the expression of matrix metalloproteinase (MMP)-2 and -9 was determined at the mRNA and protein level following treatment with PS VII. Mitogen-activated protein kinase (MAPK) expression was also detected by western blot analysis. Finally, an inhibitor of p38 MAPK was used to verify the effect of PS VII on the expression of MMP-2 and -9, as well as the migration and invasion osteosarcoma cells. This demonstrated that the proliferation, migration and invasion of the osteosarcoma cells were suppressed following treatment with PS VII. PS VII downregulated the expression of MMP-2 and -9 in a dose- and time-dependent manner. PS VII also exerted its ability to downregulate the phosphorylation of p38 MAPKs. Furthermore, by using a p38 inhibitor, SB203580, the role of PS VII in MMP-2 and -9 expression and osteosarcoma cell invasion was revealed. Taken together, these results demonstrated that PS VII suppresses the migration and invasion of osteosarcoma cells via the p38 MAPK signaling pathway.
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DOI：
10.1111/febs.13250
发表时间：
2015-05
期刊：
The FEBS journal
影响因子：
--
作者：
Gupta J;Nebreda AR
通讯作者：
Nebreda AR
影响因子：
4
作者：
Thompson, N;Lyons, J
通讯作者：
Lyons, J
重楼皂苷VII通过Ras信号通路抑制结直肠癌细胞生长
影响因子：
5.8
作者：
Li, Yuhua;Sun, Yang;Mei, Qibing
通讯作者：
Mei, Qibing
影响因子：
5
作者：
Mohseny, Alexander B.;Machado, Isidro;Cleton-Jansen, Anne-Marie
通讯作者：
Cleton-Jansen, Anne-Marie
影响因子：
2.9
作者：
Poudel B;Kim DK;Ki HH;Kwon YB;Lee YM;Kim DK
通讯作者：
Kim DK