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2015 ; 15
(ä): 814
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Incarvine C suppresses proliferation and vasculogenic mimicry of hepatocellular
carcinoma cells via targeting ROCK inhibition
#MMPMID26510899
Zhang JG
; Zhang DD
; Wu X
; Wang YZ
; Gu SY
; Zhu GH
; Li XY
; Li Q
; Liu GL
BMC Cancer
2015[Oct]; 15
(ä): 814
PMID26510899
show ga
BACKGROUND: Studies have described vasculogenic mimicry (VM) as an alternative
circulatory system to blood vessels in multiple malignant tumor types, including
hepatocellular carcinoma (HCC). In the current study, we aimed to seek novel and
more efficient treatment strategies by targeting VM and explore the underlying
mechanisms in HCC cells. METHODS: Cell counting kit-8 (CCK-8) assay and colony
survival assay were performed to explore the inhibitory effect of incarvine C
(IVC) on human cancer cell proliferation. Flow cytometry was performed to analyze
the cell cycle distribution after DNA staining and cell apoptosis by the Annexin
V-PE and 7-AAD assay. The effect of IVC on Rho-associated, coiled-coil-containing
protein kinase (ROCK) was determined by western blotting and stress fiber
formation assay. The inhibitory role of IVC on MHCC97H cell VM formation was
determined by formation of tubular network structures on Matrigel in vitro, real
time-qPCR, confocal microscopy and western blotting techniques. RESULTS: We
explored an anti-metastatic HCC agent, IVC, derived from traditional Chinese
medicinal herbs, and found that IVC dose-dependently inhibited the growth of
MHCC97H cells. IVC induced MHCC97H cell cycle arrest at G1 transition, which was
associated with cyclin-dependent kinase 2 (CDK-2)/cyclin-E1 degradation and
p21/p53 up-regulation. In addition, IVC induced apoptotic death of MHCC97H cells.
Furthermore, IVC strongly suppressed the phosphorylation of the ROCK substrate
myosin phosphatase target subunit-1 (MYPT-1) and ROCK-mediated actin fiber
formation. Finally, IVC inhibited cell-dominant tube formation in vitro, which
was accompanied with the down-regulation of VM-key factors as detected by real
time-qPCR and immunofluorescence. CONCLUSIONS: Taken together, the effective
inhibitory effect of IVC on MHCC97H cell proliferation and neovascularization was
associated with ROCK inhibition, suggesting that IVC may be a new potential drug
candidate for the treatment of HCC.