Abstract
BackgroundStudies 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.MethodsCell 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.ResultsWe 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.ConclusionsTaken 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.
Highlights
Studies have described vasculogenic mimicry (VM) as an alternative circulatory system to blood vessels in multiple malignant tumor types, including hepatocellular carcinoma (HCC)
incarvine C (IVC) inhibits the proliferation of human cancer cells Uncontrolled proliferation and robust angiogenesis (i.e. VM) contribute to the growth and metastasis of cancers
IVC affects cell cycle progression of MHCC97H cells To investigate the mechanism of the inhibitory effect of IVC on MHCC97H cell growth, flow cytometry was performed to analyze the cell cycle distribution after DNA staining
Summary
Studies have described vasculogenic mimicry (VM) as an alternative circulatory system to blood vessels in multiple malignant tumor types, including hepatocellular carcinoma (HCC). Hepatocellular carcinoma (HCC) is the sixth most common malignancy and the third most common cause of cancer-related deaths [1]. Uncontrolled tumor growth, metastasis and the absence of effective therapeutics account for the poor overall survival (OS) of HCC patients. Angiogenesis is required for metastasis [3, 4], and several mechanisms of tumor vessel formation have been proposed, including vasculogenesis, angiogenesis, intussusceptions, vascular cooption and vasculogenic mimicry (VM). Studies have described VM as an alternative circulatory system to blood vessels in multiple malignant tumor types, including HCC [6]
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Free) 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a call
