* Bufalin inhibits migration and invasion in human hepatocellular carcinoma SK-Hep1 cells through the inhibitions of NF-kB and matrix metalloproteinase-2/-9-signaling pathways.
- Metastasis plays an important role in mortality of cancer patients. Migration and invasion are the major characteristics of tumor metastasis. The induction of matrix metalloproteinases (MMPs) such as MMP-2 and -9 are particularly important for the invasiveness of various cancer cells. Bufalin, a class of toxic steroids, was purified from the skin glands of Bufo gargarizans or Bufo melanostictus; it is known to inhibit proliferation of human cancer cells. In this study, we investigated the antiinvasive mechanisms of bufalin in the human hepatocellular cancer cell line SK-Hep1. Bufalin significantly reduced serum-induced cell invasion and migration. Furthermore, bufalin markedly inhibited MMP-2 and -9 activity, mRNA expression and protein levels in SK-Hep1 cells. Bufalin attenuated phosphoinisitide-3-kinase (PI3K) and phosphorylation of AKT which was associated with reduced levels of nuclear factor kappa B (NF-κB). Bufalin also suppressed protein levels of FAK and Rho A, VEGF, MEKK3, MKK7, and uPA and it diminished NF-κB translocation. Based on these observations, we propose that bufalin is acts as an antiinvasive agent by inhibiting MMP-2 and -9 and involving PI3K/AKT and NF-κB pathways. Bufalin is a potential therapeutic agent that may have efficacy in preventing the invasion and metastasis of malignant liver tumors.
Overview of noun level
The noun level has 8 senses (first 6 from tagged texts)
1. (69) degree, grade, level -- (a position on a scale of intensity or amount or quality; "a
moderate grade of intelligence"; "a high level of care is required"; "it is all a matter of degree")
2. (22) grade, level, tier -- (a relative position or degree of value in a graded group; "lumber of
the highest grade")
3. (15) degree, level, stage, point -- (a specific identifiable position in a continuum or series or
especially in a process; "a remarkable degree of frankness"; "at what stage are the social
sciences?")
4. (5) level -- (height above ground; "the water reached ankle level"; "the pictures were at the
same level")
5. (1) level, spirit level -- (indicator that establishes the horizontal when a bubble is centered
in a tube of liquid)
6. (1) horizontal surface, level -- (a flat surface at right angles to a plumb line; "park the car
on the level")
7. level, layer, stratum -- (an abstract place usually conceived as having depth; "a good actor
communicates on several levels"; "a simile has at least two layers of meaning"; "the mind functions
on many strata simultaneously")
8. floor, level, storey, story -- (a structure consisting of a room or set of rooms at a single
position along a vertical scale; "what level is the office on?")
Overview of verb level
The verb level has 6 senses (first 3 from tagged texts)
1. (4) level -- (aim at; "level criticism or charges at somebody")
2. (1) level, raze, rase, dismantle, tear down, take down, pull down -- (tear down so as to make
flat with the ground; "The building was levelled")
3. (1) flush, level, even out, even -- (make level or straight; "level the ground")
4. charge, level, point -- (direct into a position for use; "point a gun"; "He charged his weapon at
me")
5. level -- (talk frankly with; lay it on the line; "I have to level with you")
6. level, level off -- (become level or even; "The ground levelled off")
--- WordNet end ---