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author:("Shan, xihu")
1.  Ginsenoside Rg3 inhibits epithelial-mesenchymal transition (EMT) and invasion of lung cancer by down-regulating FUT4 
Oncotarget  2015;7(2):1619-1632.
The epithelial-mesenchymal transition (EMT) is an important factor in lung cancer metastasis, and targeting EMT is a potential therapeutic strategy. Fucosyltransferase IV (FUT4) and its synthetic cancer sugar antigen Lewis Y (LeY) was abnormally elevated in many cancers. In this study, a traditional Chinese medicine ginsenoside Rg3 was used to investigate whether its inhibition to EMT and invasion of lung cancer is by the glycobiology mechanism. We found that Rg3 treatment (25, 50, 100 μg/ml) inhibited cell migration and invasion by wound-healing and transwell assays. Rg3 could significantly alter EMT marker proteins with increased E-cadherin, but decreased Snail, N-cadherin and Vimentin expression. Rg3 also down-regulated FUT4 gene and protein expression in lung cancer cells by qPCR, Western blot and immunofluorescence. After FUT4 down-regulated with shFUT4, EMT was obviously inhibited. Furthermore, the activation of EGFR through decreased LeY biosynthesis was inhibited, which blocked the downstream MAPK and NF-κB signal pathways. In addition, Rg3 reduced tumor volume and weight in xenograft mouse model, and significantly decreased tumor metastasis nodules in lung tissues by tail vein injection. In conclusion, Rg3 inhibits EMT and invasion of lung cancer by down-regulating FUT4 mediated EGFR inactivation and blocking MAPK and NF-κB signal pathways. Rg3 may be a potentially effective agent for the treatment of lung cancer.
PMCID: PMC4811485  PMID: 26636541
Rg3; EMT; FUT4; EGFR; lung cancer
2.  MRI of High-Glucose Metabolism Tumors: a Study in Cells and Mice with 2-DG-Modified Superparamagnetic Iron Oxide Nanoparticles 
This study aims to evaluate the effect of dimercaptosuccinic acid (DMSA)-coated superparamagnetic iron oxide (γ-Fe2O3@DMSA) bearing the 2-deoxy-d-glucose (2-DG) ligand on targeting tumors with high-glucose metabolism.
γ-Fe2O3@DMSA and 2-DG-conjugated γ-Fe2O3@DMSA (γ-Fe2O3@DMSA-DG) were prepared. The glucose consumption of MDA-MB-231 and MCF-7 breast cancer cells and human mammary epithelial cells (HMEpiCs) was assessed. Cells were incubated with γ-Fe2O3@DMSA or γ-Fe2O3@DMSA-DG, and MDA-MB-231 cells which exhibited the highest glucose consumption were used in breast cancer xenografts. Tumor targeting was studied by magnetic resonance imaging and Prussian blue staining in vivo.
Glucose consumption was highest in MDA-MB-231 and lowest in HMEpiCs. In vitro, there was significant uptake of γ-Fe2O3@DMSA-DG by MDA-MB-231 and MCF-7 cells within 2 h and this was inhibited by glucose. Uptake of γ-Fe2O3@DMSA-DG was significantly higher in MDA-MB-231 compared with MCF-7 cells, and there was no obvious uptake of γ-Fe2O3@DMSA in either cell line. In vivo, γ-Fe2O3@DMSA-DG could be detected in the liver and in tumors post-injection, while γ-Fe2O3@DMSA was nearly undetectable in tumors.
2-DG-coated γ-Fe2O3@DMSA improved tumor targeting of γ-Fe2O3@DMSA which can be assessed by magnetic resonance imaging.
PMCID: PMC4722088  PMID: 26150194
2-Deoxy-d-glucose; Superparamagnetic iron oxide; Glucose metabolism; Breast cancer; Magnetic resonance imaging
3.  Ginsenoside Rg3 Inhibits Melanoma Cell Proliferation through Down-Regulation of Histone Deacetylase 3 (HDAC3) and Increase of p53 Acetylation 
PLoS ONE  2014;9(12):e115401.
Malignant melanoma is an aggressive and deadly form of skin cancer, and despite recent advances in available therapies, is still lacking in completely effective treatments. Rg3, a monomer extracted from ginseng roots, has been attempted for the treatment of many cancers. It is reported that the expressions of histone deacetylase 3 (HDAC3) and p53 acetylation correlate with tumor cell growth. However, the antitumor effect of Rg3 on melanoma and the mechanism by which it regulates HDAC3 expression and p53 acetylation remain unknown. We found high expression of HDAC3 in human melanoma tissues to be significantly correlated to lymph node metastasis and clinical stage of disease (p<0.05). In melanoma cells, Rg3 inhibited cell proliferation and induced G0/G1 cell cycle arrest. Rg3 also decreased the expression of HDAC3 and increased the acetylation of p53 on lysine (k373/k382). Moreover, suppression of HDAC3 by either siRNA or a potent HDAC3 inhibitor (MS-275) inhibited cell proliferation, increased p53 acetylation and transcription activity. In A375 melanoma xenograft studies, we demonstrated that Rg3 and HDAC3 short hairpin RNA (shHDAC3) inhibited the growth of xenograft tumors with down-regulation of HDAC3 expression and up-regulation of p53 acetylation. In conclusion, Rg3 has antiproliferative activity against melanoma by decreasing HDAC3 and increasing acetylation of p53 both in vitro and in vivo. Thus, Rg3 serves as a potential therapeutic agent for the treatment of melanoma.
PMCID: PMC4270766  PMID: 25521755
4.  Effects of axon degeneration on oligodendrocyte lineage cells: Dorsal rhizotomy evokes a repair response while axon degeneration rostral to spinal contusion induces both repair and apoptosis 
Glia  2010;58(11):1304-1319.
Wallerian degeneration in the dorsal columns (DC) after spinal cord injury (SCI) is associated with microglial activation and prolonged oligodendrocyte (OL) apoptosis that may contribute to demyelination and dysfunction after SCI. But, there is an increase in OL lineage cells after SCI that may represent a reparative response, and there is evidence for remyelination after SCI. To assess the role of axonal degeneration per se in OL apoptosis and proliferation, we cut the L2-S2 dorsal roots producing massive axonal degeneration and microglial activation in the DC, and found no evidence of OL loss or apoptosis. Rather, the numbers of OL-lineage cells positive for NG2 and APC (CC1) increased, and BrdU studies suggested new OL formation. We then tested contusion SCI (cSCI) that results in comparable degeneration in the DC rostral to the injury, microglial activation, and apoptosis of DC OLs by 8 days. NG2+ cell proliferation and oligodendrogenesis was seen as after rhizotomy. The net result of this combination of proliferation and apoptosis was a reduction in DC OLs, confirming earlier studies. Using an antibody to oxidized nucleic acids, we found rapid and prolonged RNA oxidation in OLs rostral to cSCI, but no evidence of oxidative stress in DC OLs after rhizotomy. These results suggest that signals associated with axonal degeneration are sufficient to induce OL proliferation, and that secondary injury processes associated with the central SCI, including oxidative stress, rather than axonal degeneration per se, are responsible for OL apoptosis.
PMCID: PMC3045846  PMID: 20607865
cell death; cell proliferation; progenitor cells; Wallerian degeneration; spinal cord injury; dorsal root; dorsal columns; oxidative stress
5.  Messenger RNA Oxidation Occurs Early in Disease Pathogenesis and Promotes Motor Neuron Degeneration in ALS 
PLoS ONE  2008;3(8):e2849.
Accumulating evidence indicates that RNA oxidation is involved in a wide variety of neurological diseases and may be associated with neuronal deterioration during the process of neurodegeneration. However, previous studies were done in postmortem tissues or cultured neurons. Here, we used transgenic mice to demonstrate the role of RNA oxidation in the process of neurodegeneration.
Methodology/Principal Findings
We demonstrated that messenger RNA (mRNA) oxidation is a common feature in amyotrophic lateral sclerosis (ALS) patients as well as in many different transgenic mice expressing familial ALS-linked mutant copper-zinc superoxide dismutase (SOD1). In mutant SOD1 mice, increased mRNA oxidation primarily occurs in the motor neurons and oligodendrocytes of the spinal cord at an early, pre-symptomatic stage. Identification of oxidized mRNA species revealed that some species are more vulnerable to oxidative damage, and importantly, many oxidized mRNA species have been implicated in the pathogenesis of ALS. Oxidative modification of mRNA causes reduced protein expression. Reduced mRNA oxidation by vitamin E restores protein expression and partially protects motor neurons.
These findings suggest that mRNA oxidation is an early event associated with motor neuron deterioration in ALS, and may be also a common early event preceding neuron degeneration in other neurological diseases.
PMCID: PMC2481395  PMID: 18682740

Results 1-5 (5)