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Melatonin inhibits chondrosarcoma cell metastasis by suppressing MMP7 expression

為了解決中國醫藥大學pcr的問題，作者NGUYEN BAO TRAN 這樣論述：

Chondrosarcoma is rare but has intense metastasis and limited response to chemotherapy and radiation treatment. Enzymatic activity of matrix metalloproteinase (MMP) family members has an important role in chondrosarcoma metastasis. Melatonin exhibits anticarcinogenic activity in many types of cance

rs by suppressing the expression of certain MMP family members, but this has not been clearly determined as yet in chondrosarcoma. Using a human protease array kit, this study analyzed the protein expression of two chondrosarcoma cell lines (JJ012 and SW1353) with and without melatonin treatment, re

vealing that matrix metalloproteinase-7 (MMP7) was among the top three proteins suppressed by melatonin. Further cell experiments showed that melatonin effectively suppresses proliferative and metastatic activities in chondrosarcoma cells. Moreover, melatonin suppressed anoikis resistance, as determ

ined by anchorage-independent growth under suspension conditions in an anoikis assay and by low quantities of chondrosarcoma cells in the circulation of an in vivo study. In nude BALB/c mice, melatonin significantly inhibited tumor growth and lung metastases. Cell culture revealed that overexpressio

n of MMP7 significantly promoted chondrosarcoma cell proliferation and migration, which was significantly inhibited by melatonin. A subsequent tissue array demonstrated significantly higher levels of MMP7 expression in chondrosarcoma tissue compared with normal cartilage tissue specimens; chondrosar

coma disease stage/grade was correlated with MMP7 expression. Next, a comparison of micro-RNA (miRNA) expression profiles of melatonin-treated and melatonin-untreated chondrosarcoma cells identified that several miRNAs were up-regulated in the melatonin-treated cells. A computational prediction was

performed using four publicly available miRNA databases (TargetScan, miRanda, miRMap and miRWalk) to predict miRNA targeting MMP7. The intersection of 11 candidate miRNAs identified miR-520f-3p as the most up-regulated miRNA in response to melatonin. Thus, our study suggests that melatonin reduces M

MP7 synthesis, chondrosarcoma cell motility and metastasis via the miR-520f-3p/MMP7 axis.Keywords: Chondrosarcoma, proliferation, metastasis, melatonin, MMP7, miR-520f-3p