Xiangyong Li

Publications (8)20.97 Total impact

• Article: Sirolimus ameliorates inflammatory responses by switching the Treg/Th17 profile in murine colitis.

  Hui Yin, Xiangyong Li, Bobin Zhang, Tao Liu, Baohong Yuan, Qian Ni, Shilian Hu, Hongbiao Gu
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  ABSTRACT: Inflammatory bowel disease (IBD) is characterized by dysregulated immune responses in inflamed intestine, with dominance of IL-17-producing cells and deficiency of Treg cells. The aim of this study was to investigate the effect and mechanisms of sirolimus, an inhibitor of the mammalian target of rapamycin (mTOR), on immune responses in a murine model of Crohn's disease (CD). Murine colitis was induced by intrarectal administration with 2,4,6-trinitrobenzene sulfonic acid (TNBS) at day 0. Mice were then i.p.-treated with sirolimus daily for three days. The gross and histological appearances of the colon and the numbers, phenotype and cytokine production of lymphocytes were compared with these characteristics in a control group. Sirolimus treatment significantly decreased all macroscopic, microscopic and histopathologic parameters of colitis analyzed. The therapeutic effects of sirolimus were associated with a down-regulation of proinflammatory cytokines TNF-α, IL-6 and IL-17A. Intriguingly, sirolimus administration resulted in a prominent up-regulation of regulatory cytokine TGF-β. Supporting the hypothesis that sirolimus directly affects functional activity of CD4+ CD25+ Treg cells, we observed a remarkable enhancement of FoxP3 expression in colon tissues and isolated CD4+ T cells of sirolimus-treated mice. Simultaneously, sirolimus treatment led to a significant reduction in the number of CD4+ IL-17A+ T cells in the MLN cells as well as IL-17A production in MLN cells. Therefore, sirolimus may offer a promising new therapeutic strategy for the treatment of IBD. © 2013 The Authors. Immunology © 2013 Blackwell Publishing Ltd.
  Immunology 03/2013; · 3.32 Impact Factor
• Article: (-)-Epigallocatechin-3-gallate inhibits human papillomavirus (HPV)-16 oncoprotein-induced angiogenesis in non-small cell lung cancer cells by targeting HIF-1α

  Li He, Erying Zhang, Jingli Shi, Xiangyong Li, Keyuan Zhou, Qunzhou Zhang, Anh D Le, Xudong Tang
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  ABSTRACT: PURPOSE: To investigate the effects of (-)-epigallocatechin-3-gallate (EGCG) on human papillomavirus (HPV)-16 oncoprotein-induced angiogenesis in non-small cell lung cancer (NSCLC) cells and the underlying mechanisms. METHODS: NSCLC cells (A549 and NCI-H460) transfected with EGFP plasmids containing HPV-16 E6 or E7 oncogene were treated with different concentrations of EGCG for 16 h. The effects of EGCG on angiogenesis in vitro and in vivo were observed. The expression of HIF-1α, p-Akt, and p-ERK1/2 proteins in NSCLC cells was analyzed by Western blot. The levels of HIF-1α mRNA in NSCLC cells were detected by real-time RT-PCR. The concentration of VEGF and IL-8 in the conditioned media was determined by ELISA. HIF-1α, VEGF, and CD31 expression in A549 xenografted tumors of nude mice was analyzed by immunohistochemistry. RESULTS: HPV-16 E6 and E7 oncoproteins HIF-1α-dependently promoted angiogenesis in vitro and in vivo, which was inhibited by EGCG. Mechanistically, EGCG inhibited HPV-16 oncoprotein-induced HIF-1α protein expression but had no effect on HIF-1α mRNA expression in NSCLC cells. Additionally, 50 and 100 μmol/L of EGCG significantly reduced the secretion of VEGF and IL-8 proteins induced by HPV-16 E7 oncoprotein in NSCLC A549 cells. Meanwhile, HPV-16 E6 and E7 oncoproteins HIF-1α-dependently enhanced Akt activation in A549 cells, which was suppressed by EGCG. Furthermore, EGCG inhibited HPV-16 oncoprotein-induced HIF-1α and HIF-1α-dependent VEGF and CD31 expression in A549 xenografted tumors. CONCLUSIONS: EGCG inhibited HPV-16 oncoprotein-induced angiogenesis conferred by NSCLC through the inhibition of HIF-1α protein expression and HIF-1α-dependent expression of VEGF, IL-8, and CD31 as well as activation of Akt, suggesting that HIF-1α may be a potential target of EGCG against HPV-related NSCLC angiogenesis.
  Cancer Chemotherapy and Pharmacology 01/2013; · 2.83 Impact Factor
• Article: Norathyriol suppresses transformation in JB6 P+ cells by the inhibition of Akt.

  Jixia Li, Xiangyong Li, Zhiwei He, Keyuan Zhou
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  ABSTRACT: Context: Chemoprevention has been acknowledged as an important and practical strategy for the management of skin cancer. Norathyriol, a naturally occurring compound present in various plants, has a potent anticancer-promoting activity. Aims: The aim was to investigate the chemopreventive activity of norathyriol on JB6 P+ cells. Materials and Methods: A soft agar assay was used to detect the effect of norathyriol on cell transformation. The activator protein-1 (AP-1) transactivation activity was examined by the luciferase assay. Results: Norathyriol inhibited epidermal growth factor (EGF)- and 12-O-tetradecanoylphorbol-13-acetate (TPA)-induced neoplastic cell transformation in a dose-dependent manner. The activation of activator protein-1 was dose dependently suppressed by norathyriol treatment. Western blot data revealed that norathyriol attenuated the phosphorylation of Akt. Conclusions: Norathyriol exerts a potent chemopreventive activity by inhibiting Akt activation in neoplastic cell transformation.
  Journal of cancer research and therapeutics 10/2012; 8(4):561-4. · 0.83 Impact Factor
• Article: Heme oxygenase-1 ameliorates LPS-induced acute lung injury correlated with downregulation of interleukin-33.

  Hui Yin, Xiangyong Li, Baohong Yuan, Bobin Zhang, Shilian Hu, Hongbiao Gu, Xiaobao Jin, Jiayong Zhu
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  ABSTRACT: Although studies have shown that heme oxygenase-1 (HO-1) can abrogate leukocyte recruitment and tissue injury after LPS stimulation, the underlying mechanisms remain incompletely understood. Interleukin (IL)-33, a new member of the IL-1 family, is found to play a crucial immunoregulatory effect on the MD2/TLR4 complex expression. Moreover, TLR4 further promotes the activation of NF-κB and the production of proinflammatory mediators, which exacerbate neutrophil infiltration and organ damage. The present study was designed to determine whether the protection of HO-1 against LPS-induced acute lung injury (ALI) is involved in downregulation of IL-33. We observed that the levels of IL-33 mRNA and protein in LPS-stimulated macrophages were strongly suppressed by a potent HO-1 inducer, CoPP, treatment. Meanwhile, CoPP significantly reduced the expression of TLR4 and TNF-α in IL-33-pretreated macrophages followed LPS challenge. In the murine model of LPS-induced ALI, CoPP treatment resulted in a remarkable decrease in LPS-mediated leukocyte exudation, Evans blue dye albumin (EBA) leakage as well as histopathologic disruption. Notably, CoPP treatment markedly inhibited the expression of IL-33 and TLR4 in lung tissues under LPS stimulation. Therefore, these data suggest that the cytoprotection of HO-1 in LPS-induced pulmonary injury is associated with negative regulation of IL-33 and TLR4-mediated inflammatory response.
  International immunopharmacology 09/2011; 11(12):2112-7. · 2.21 Impact Factor
• Article: Heme oxygenase-1 upregulation improves lipopolysaccharide-induced acute lung injury involving suppression of macrophage migration inhibitory factor.

  Hui Yin, Xiangyong Li, Quan Gong, Xiaobao Jin, Hongbiao Gu, Baohong Yuan, Bobin Zhang, Fang Zheng, Feili Gong, Jiayong Zhu
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  ABSTRACT: Although studies have demonstrated that heme oxygenase-1 (HO-1) prevents leukocyte infiltration and organ damage following LPS challenge, the mechanisms involved in this protection are incompletely understood. Macrophage migration inhibitory factor (MIF) is thought to play a pivotal role in modulation of inflammatory and immune response through upregulation of TLR4 expression. Activation of TLR4 results in the production of proinflammatory mediators including MIF, which induce neutrophils recruitment and subsequent tissue insults. We hypothesized that HO-1 mediates its salutary effects in lipopolysaccharide (LPS)-induced inflammatory lung injury via downregulation of MIF through modulation of TLR4-induced proinflammatory mediator production. Compared with wild-type cells, MIF-knockdown macrophages in vitro are hyporesponsive to LPS stimulation, as shown by a profound reduction in TLR4 expression and TNF-alpha production. In the murine model of LPS-induced acute lung injury, administration of CoPP, a potent HO-1 inducer, leaded to a significant reduction in LPS-induced pulmonary edema, leucocytes influx, myeloperoxidase activity as well as histopathologic insults. Most strikingly, pretreatment with CoPP markedly decreased the expression of TLR4 and MIF in lung tissues in response to LPS challenge. These findings herein suggest that the cytoprotective functions of HO-1 in LPS-induced lung injury are associated with negative regulation of lung MIF and TLR4-induced inflammatory response.
  Molecular Immunology 09/2010; 47(15):2443-9. · 2.90 Impact Factor
• Article: Bax inhibitor-1 mediates apoptosis-resistance in human nasopharyngeal carcinoma cells.

  Meihong Zhang, Xiangyong Li, Yuefei Zhang, Keyuan Zhou
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  ABSTRACT: Bax inhibitor-1 (BI-1), a newly identified apoptosis inhibitor, has recently been found to be overexpressed in several human carcinomas and its specific down-regulation by RNA interference (RNAi) could lead to cell death. The purpose of this study is to investigate the role of BI-1 in apoptosis-resistance and the underlying mechanisms in human nasopharyngeal carcinoma (NPC) cells. Our results showed that BI-1 was expressed in two different human NPC cell lines, CNE-2Z and CNE-1, and specific inhibition of BI-1 expression by siRNA caused a significant increase in spontaneous apoptosis in both cell lines. Mechanistically, we demonstrated that down-regulation of BI-1 protein expression decreased the ratio of Bcl-X(L)/Bcl-2 with Bax protein as determined by Western blot and increased the activity of caspase-3 by colorimetric analysis, thus leading to the activation of the associated cell death pathways. Taken together, these results have provided evidence that BI-1 could serve as an important molecular target gene for the development of new therapeutic strategy against human NPCs.
  Molecular and Cellular Biochemistry 08/2009; 333(1-2):1-7. · 2.06 Impact Factor
• Article: Bisphosphonates suppress insulin-like growth factor 1-induced angiogenesis via the HIF-1alpha/VEGF signaling pathways in human breast cancer cells.

  Xudong Tang, Qunzhou Zhang, Shihong Shi, Yun Yen, Xiangyong Li, Yuefei Zhang, Keyuan Zhou, Anh D Le
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  ABSTRACT: Adjunctive chemotherapy with bisphosphonates has been reported to delay bone metastasis and improve overall survival in breast cancer. Aside from its antiresorptive effect, bisphosphonates exhibit antitumor activities, in vitro and in vivo, via several mechanisms, including antiangiogenesis. In this study, we investigated the potential molecular mechanisms underlying the antiangiogenic effect of non-nitrogen-containing and nitrogen-containing bisphosphonates, clodronate and pamidronate, respectively, in insulin-like growth factor (IGF)-1 responsive human breast cancer cells. We tested whether bisphosphonates had any effects on hypoxia-inducible factor (HIF)-1alpha/vascular endothelial growth factor (VEGF) axis that plays a pivotal role in tumor angiogenesis, and our results showed that both pamidronate and clodronate significantly suppressed IGF-1-induced HIF-1alpha protein accumulation and VEGF expression in MCF-7 cells. Mechanistically, we found that either pamidronate or clodronate did not affect mRNA expression of HIF-1alpha, but they apparently promoted the degradation of IGF-1-induced HIF-1alpha protein. Meanwhile, we found that the presence of pamidronate and clodronate led to a dose-dependent decease in the newly-synthesized HIF-1alpha protein induced by IGF-1 in breast cancer cells after proteasomal inhibition, thus, indirectly reflecting the inhibition of protein synthesis. In addition, our results indicated that the inhibitory effects of bisphosphonates on the HIF-1alpha/VEGF axis are associated with the inhibition of the phosphoinositide 3-kinase/AKT/mammalian target of rapamycin signaling pathways. Consistently, we demonstrated that pamidronate and clodronate functionally abrogated both in vitro and in vivo tumor angiogenesis induced by IGF-1-stimulated MCF-7 cells. These findings have highlighted an important mechanism of the pharmacological action of bisphosphonates in the inhibition of tumor angiogenesis in breast cancer cells.
  International Journal of Cancer 07/2009; 126(1):90-103. · 5.44 Impact Factor
• Article: Overexpression of PTEN induces cell growth arrest and apoptosis in human breast cancer ZR-75-1 cells.

  Xiangyong Li, Guanping Lin, Binhua Wu, Xin Zhou, Keyuan Zhou
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  ABSTRACT: Phosphatase and tensin homolog (PTEN) is a tumor suppressor gene located at human chromosome 10q23, might play an important role in cell proliferation, cell cycle and apoptosis of cancer cells. In this study, the eukaryotic expression vectors pBP-wt-PTEN (containing a wild-type PTEN gene) and pBP-G129R-PTEN (containing a mutant PTEN gene) were used to transfect breast cancer ZR-75-1 cells. After transfection, ZR-75-1 cells expressing PTEN were obtained and tested. The blue exclusion assay showed the growth rate of the cells transfected with pBP-wt-PTEN was significantly lower than that of the control cells transfected with pBP-G129R-PTEN. Analysis of the cell cycle by flow cytometry showed that the progression from the G(1) to the S phase was arrested in cells expressing wild-type PTEN. Some typical morphological changes of apoptosis were also observed in cells transfected with pBP-wt-PTEN, but not in those transfected with pBP-G129R-PTEN. This study shows that overexpression of PTEN in ZR-75-1 cells leads to cell growth arrest and apoptosis.
  Acta Biochimica et Biophysica Sinica 11/2007; 39(10):745-50. · 1.38 Impact Factor