• Molecules and Cells
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• v.40 no.10
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• pp.761-772
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• 2017

Glioblastoma is the most frequent and most aggressive brain tumor in adults. Solute carrier family 8 member 2 (SLC8A2) is only expressed in normal brain, but not present in other human normal tissues or in gliomas. Therefore, we hypothesized that SLC8A2 might be a glioma tumor suppressor gene and detected the role of SLC8A2 in glioblastoma and explored the underlying molecular mechanism. The glioblastoma U87MG cells stably transfected with the lentivirus plasmid containg SLC8A2 (U87MG-SLC8A2) and negative control (U87MG-NC) were constructed. In the present study, we found that the tumorigenicity of U87MG in nude mice was totally inhibited by SLC8A2. Overexpression of SLC8A2 had no effect on cell proliferation or cell cycle, but impaired the invasion and migration of U87MG cells, most likely through inactivating the extracellular signal-related kinases (ERK)1/2 signaling pathway, inhibiting the nuclear translocation and DNA binding activity of nuclear factor kappa B ($NF-{\kappa}B$), reducing the level of matrix metalloproteinases (MMPs) and urokinase-type plasminogen activator (uPA)-its receptor (uPAR) system (ERK1/2-$NF-{\kappa}B$-MMPs/uPA-uPAR), and altering the protein levels of epithelial to mesenchymal transitions (EMT)-associated proteins E-cardherin, vimentin and Snail. In addition, SLC8A2 inhibited the angiogenesis of U87MG cells, probably through combined inhibition of endothelium-dependent and endothelium-nondependent angiogenesis (vascular mimicry pattern). Totally, SLC8A2 serves as a tumor suppressor gene and inhibits invasion, angiogenesis and growth of glioblastoma.

• Asian Pacific Journal of Cancer Prevention
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• v.15 no.15
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• pp.6219-6225
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• 2014

Background: Increasing evidence from animal, epidemiological and clinical investigations suggest that dietary anthocyanins have potential to prevent chronic diseases, including cancers. It is also noteworthy that human epidermal growth factor receptor 2 (ErbB2) protein overexpression or ErbB2 gene amplification has been included as an indicator for metastasis and higher risk of recurrence for breast cancer. Materials and Methods: The present experiments investigated the anti-metastasis effects of black rice anthocyanins (BRACs) on ErbB2 positive breast cancer cells in vivo and in vitro. Results: Oral administration of BRACs (150 mg/kg/day) reduced transplanted tumor growth, inhibited pulmonary metastasis, and decreased lung tumor nodules in BALB/c nude mice bearing ErbB2 positive breast cancer cell MDA-MB-453 xenografts. The capacity for migration, adhesion, motility and invasion was also inhibited by BRACs in MDA-MB-453 cells in a concentration dependent manner, accompanied by decreased activity of a transfer promoting factor, urokinase-type plasminogen activator (u-PA). Conclusions: Together, our results indicated that BRACs possess anti-metastasis potential against ErbB2 positive human breast cancer cells in vivo and in vitro through inhibition of metastasis promoting molecules.

• Childhood Kidney Diseases
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• v.8 no.1
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• pp.26-32
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• 2004

Purpose : Hypercoagulability is present in patients with nephrotic syndrome. Plasminogen activator inhibitor type 1(PAI-1) is a major inhibitor of plasminogen activators. PAI-1 inactivates both tissue plasminogen activator(tPA) and urokinase plasminogen activator(uPA) by rapid formation of inactive 1:1 stoichiometric complexes. Recently some studies showed that the enhanced PAI-1 expression may be involved in the intraglomerular fibrinogen/fibrinrelated antigen deposition seen in nephrotic syndrome. Methods : PAI-1 gene promoter -844(G/A) polymorphism was evaluated in 146 children with minimal change nephrotic syndrome(MCNS) and 230 control subjects. The patients with MCNS were subdivided into 85 infrequent-relapser(IR) group and 61 frequent relapser(FR) group. PCR of PAI-1 gene promoter region including -844(G/A) and RFLP using the restriction enzyme Xhol were performed for each DNA samples extracted from the groups. Results : The distribution of PAI-1 genotype in the control group was G/G 81(32.5%), A/A 42(16.9%), and G/A 126(50.6%). The distribution of PAI-1 genotypes in the IR group of MCNS was G/G 29(34.1%), A/A 15(17.7%), and G/A 41(48.2%). The distribution of PAI-1 genotype in the FR group of MCNS was G/G 17(27.9%), A/A 18(29.5%), and G/A 26(42.6%). There was a significantly increased frequency of A/A genotype(P=0.0251) in the FR group of MCNS. Conclusion : Our results indicate that the PAI-1 gene promoter A/A genotype may be associated with the FR in MCNS.