1. LFG-500 inhibits the invasion of cancer cells via down-regulation of PI3K/AKT/NF-κB signaling pathway.
- Author
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Li C, Li F, Zhao K, Yao J, Cheng Y, Zhao L, Li Z, Lu N, and Guo Q
- Subjects
- Allografts, Animals, Cell Adhesion drug effects, Cell Line, Tumor, Cell Movement drug effects, Down-Regulation, Enzyme Activation drug effects, Humans, Male, Matrix Metalloproteinase 2 metabolism, Matrix Metalloproteinase 9 metabolism, Melanoma, Experimental drug therapy, Melanoma, Experimental metabolism, Melanoma, Experimental pathology, Mice, NF-kappa B genetics, Protein Transport, STAT3 Transcription Factor metabolism, Transcription Factor AP-1 metabolism, Transcriptional Activation drug effects, Tumor Burden drug effects, Antineoplastic Agents pharmacology, Flavonoids pharmacology, NF-kappa B metabolism, Phosphatidylinositol 3-Kinases metabolism, Proto-Oncogene Proteins c-akt metabolism, Signal Transduction drug effects
- Abstract
Cancer cell invasion, one of the crucial events in local growth and metastatic spread of tumors, possess a broad spectrum of mechanisms, especially altered expression of matrix metalloproteinases. LFG-500 is a novel synthesized flavonoid with strong anti-cancer activity, whose exact molecular mechanism remains incompletely understood. This current study was designed to examine the effects of LFG-500 on tumor metastasis using in vitro and in vivo assays. LFG-500 could inhibit adhesion, migration and invasion of MDA-MB-231 human breast carcinoma cells. Meanwhile, it reduced the activities and expression of MMP-2 and MMP-9 via suppressing the transcriptional activation of NF-κB rather than AP-1 or STAT3. Moreover, LFG-500 repressed TNF-α induced cell invasion through inhibiting NF-κB and subsequent MMP-9 activity. Further elucidation of the mechanism revealed that PI3K/AKT but not MAPK signaling pathway was involved in the inhibitory effect of LFG-500 on NF-κB activation. LFG-500 could also suppress lung metastasis of B16F10 murine melanoma cells in vivo. Taken together, these results demonstrated that LFG-500 could block cancer cell invasion via down-regulation of PI3K/AKT/NF-κB signaling pathway, which provides new evidence for the anti-cancer activity of LFG-500.
- Published
- 2014
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