期刊论文详细信息
BMC Complementary and Alternative Medicine
Bidirectional regulation of angiogenesis and miR-18a expression by PNS in the mouse model of tumor complicated by myocardial ischemia
Teng Zhang2  Yu Chen2  Wenjian Wang2  Li Li2  Bingbing Ning1  Li Liu1  Chenglin Jia1  Minqi Xiong1  Peiwei Wang2  Jingang Cui2  Xiaoyan Wang1  Qinbo Yang2 
[1] Yueyang Hospital, Shanghai University of TCM, 110 Ganhe Rd, Shanghai 200437, China;Clinical Research Institute of Integrative Medicine, Shanghai University of Traditional Chinese Medicine, Shanghai Academy of Traditional Chinese Medicine, 110 Ganhe Rd, Shanghai 200437, China
关键词: miR-18a;    Bidirectional regulation;    PNS;    Angiogenesis;    Tumor;    Myocardial ischemia;   
Others  :  1220110
DOI  :  10.1186/1472-6882-14-183
 received in 2014-01-13, accepted in 2014-05-29,  发布年份 2014
PDF
【 摘 要 】

Background

Panax Notoginseng Saponins (PNS) is the major class of active constituents of notoginseng, a natural product extensively used as a therapeutic agent in China. Tumor when accompanied by cardiovascular disorders poses a greater challenge for clinical management given the paradoxical involvement of angiogenesis, therefore gaining increased research attention. This study aim to investigate effects of PNS and its activity components in the mouse model of tumor complicated with myocardial ischemia.

Methods

Tumor complexed with myocardial ischemia mouse model was first established, which was followed by histological and immunohistochemistry examination to assess the effect of indicated treatments on tumor, myocardial ischemia and tissue specific angiogenesis. MicroRNA (miRNA) profiling was further carried out to identify potential miRNA regulators that might mechanistically underline the therapeutic effects of PNS in this complex model.

Results

PNS and its major activity components Rg1, Rb1 and R1 suppressed tumor growth and simultaneously attenuated myocardial ischemia. PNS treatment led to decreased expression of CD34 and vWF in tumor and increased expression of these vascular markers in heart. PNS treatment resulted in reduced expression of miR-18a in tumor and upregulated expression of miR-18a in heart.

Conclusions

Our data demonstrated for the first time that PNS exerts tissue specific regulatory effects on angiogenesis in part through modulating the expression of miR-18a, which could be responsible for its bidirectional effect on complex disease conditions where paradoxical angiogenesis is implicated. Therefore, our study provides experimental evidence warranting evaluation of PNS and related bioactive component as a rational therapy for complex disease conditions including co-manifestation of cancer and ischemic cardiovascular disease.

【 授权许可】

   
2014 Yang et al.; licensee BioMed Central Ltd.

【 预 览 】
附件列表
Files Size Format View
20150721072234558.pdf 2218KB PDF download
Figure 4. 625KB Image download
Figure 3. 720KB Image download
Figure 2. 375KB Image download
Figure 1. 681KB Image download
【 图 表 】

Figure 1.

Figure 2.

Figure 3.

Figure 4.

【 参考文献 】
  • [1]Wehland M, Bauer J, Magnusson NE, Infanger M, Grimm D: Biomarkers for anti-angiogenic therapy in cancer. Int J Mol Sci 2013, 14(5):9338-9364.
  • [2]Tahergorabi Z, Khazaei M: A review on angiogenesis and its assays. Iranian J Basic Med Sci 2012, 15(6):1110-1126.
  • [3]Ng TB: Pharmacological activity of sanchi ginseng (Panax notoginseng). J Pharm Pharmacol 2006, 58(8):1007-1019.
  • [4]Chen H, Yin J, Deng Y, Yang M, Xu L, Teng F, Li D, Cheng Y, Liu S, Wang D, Zhang T, Wu W, Liu X, Guan S, Jiang B, Guo D: The protective effects of ginsenoside Rg1 against hypertension target-organ damage in spontaneously hypertensive rats. BMC Compl Altern Med 2012, 12:53. BioMed Central Full Text
  • [5]Leung KW, Wong AS: Pharmacology of ginsenosides: a literature review. Chin Med 2010, 5:20. BioMed Central Full Text
  • [6]Kim JH: Cardiovascular diseases and Panax ginseng: a review on molecular mechanisms and medical applications. J Ginseng Res 2012, 36(1):16-26.
  • [7]Hong SJ, Wan JB, Zhang Y, Hu G, Lin HC, Seto SW, Kwan YW, Lin ZX, Wang YT, Lee SM: Angiogenic effect of saponin extract from Panax notoginseng on HUVECs in vitro and zebrafish in vivo. Phytother Res: PTR 2009, 23(5):677-686.
  • [8]Yu LC, Chen SC, Chang WC, Huang YC, Lin KM, Lai PH, Sung HW: Stability of angiogenic agents, ginsenoside Rg1 and Re, isolated from Panax ginseng: in vitro and in vivo studies. Int J Pharm 2007, 328(2):168-176.
  • [9]Ohashi R, Yan S, Mu H, Chai H, Yao Q, Lin PH, Chen C: Effects of homocysteine and ginsenoside Rb1 on endothelial proliferation and superoxide anion production. J Surg Res 2006, 133(2):89-94.
  • [10]Leung KW, Cheung LW, Pon YL, Wong RN, Mak NK, Fan TP, Au SC, Tombran-Tink J, Wong AS: Ginsenoside Rb1 inhibits tube-like structure formation of endothelial cells by regulating pigment epithelium-derived factor through the oestrogen beta receptor. Br J Pharmacol 2007, 152(2):207-215.
  • [11]Sun B, Xiao J, Sun XB, Wu Y: Notoginsenoside R1 attenuates cardiac dysfunction in endotoxemic mice: an insight into oestrogen receptor activation and PI3K/Akt signalling. Br J Pharmacol 2013, 168(7):1758-1770.
  • [12]Sengupta S, Toh SA, Sellers LA, Skepper JN, Koolwijk P, Leung HW, Yeung HW, Wong RN, Sasisekharan R, Fan TP: Modulating angiogenesis: the yin and the yang in ginseng. Circulation 2004, 110(10):1219-1225.
  • [13]He NW, Zhao Y, Guo L, Shang J, Yang XB: Antioxidant, antiproliferative, and pro-apoptotic activities of a saponin extract derived from the roots of Panax notoginseng (Burk.) F.H. Chen. J Med Food 2012, 15(4):350-359.
  • [14]Wang P, Cui J, Du X, Yang Q, Jia C, Xiong M, Yu X, Li L, Wang W, Chen Y, Zhang T: Panax notoginseng saponins (PNS) inhibits breast cancer metastasis. J Ethnopharmacol 2014, 30(14):00320-00325.
  • [15]Rona G, Chappel CI, Balazs T, Gaudry R: An infarct-like myocardial lesion and other toxic manifestations produced by isoproterenol in the rat. AMA Arch Pathol 1959, 67(4):443-455.
  • [16]Rona G: Catecholamine cardiotoxicity. J Mol Cell Cardiol 1985, 17(4):291-306.
  • [17]Teerlink JR, Pfeffer JM, Pfeffer MA: Progressive ventricular remodeling in response to diffuse isoproterenol-induced myocardial necrosis in rats. Circ Res 1994, 75(1):105-113.
  • [18]Zbinden G, Moe RA: Pharmacological studies on heart muscle lesions induced by isoproterenol. Ann N Y Acad Sci 1969, 156(1):294-308.
  • [19]Csapo Z, Dusek J, Rona G: Early alterations of the cardiac muscle cells in isoproterenol-induced necrosis. Arch Pathol 1972, 93(4):356-365.
  • [20]Hurwitz H, Fehrenbacher L, Novotny W, Cartwright T, Hainsworth J, Heim W, Berlin J, Baron A, Griffing S, Holmgren E, Ferrara N, Fyfe G, Rogers B, Ross R, Kabbinavar F: Bevacizumab plus irinotecan, fluorouracil, and leucovorin for metastatic colorectal cancer. N Engl J Med 2004, 350(23):2335-2342.
  • [21]Sagar SM, Yance D, Wong RK: Natural health products that inhibit angiogenesis: a potential source for investigational new agents to treat cancer-Part 1. Curr Oncol 2006, 13(1):14-26.
  • [22]Sagar SM, Yance D, Wong RK: Natural health products that inhibit angiogenesis: a potential source for investigational new agents to treat cancer-Part 2. Curr Oncol 2006, 13(3):99-107.
  • [23]Hayashita Y, Osada H, Tatematsu Y, Yamada H, Yanagisawa K, Tomida S, Yatabe Y, Kawahara K, Sekido Y, Takahashi T: A polycistronic microRNA cluster, miR-17-92, is overexpressed in human lung cancers and enhances cell proliferation. Cancer Res 2005, 65(21):9628-9632.
  • [24]Wu W, Takanashi M, Borjigin N, Ohno SI, Fujita K, Hoshino S, Osaka Y, Tsuchida A, Kuroda M: MicroRNA-18a modulates STAT3 activity through negative regulation of PIAS3 during gastric adenocarcinogenesis. Br J Cancer 2013, 108(3):653-661.
  • [25]Hirajima S, Komatsu S, Ichikawa D, Takeshita H, Konishi H, Shiozaki A, Morimura R, Tsujiura M, Nagata H, Kawaguchi T, Arita T, Kubota T, Fujiwara H, Okamoto K, Otsuji E: Clinical impact of circulating miR-18a in plasma of patients with oesophageal squamous cell carcinoma. Br J Cancer 2013, 108(9):1822-1829.
  • [26]van Almen GC, Verhesen W, van Leeuwen RE, van de Vrie M, Eurlings C, Schellings MW, Swinnen M, Cleutjens JP, van Zandvoort MA, Heymans S, Schroen B: MicroRNA-18 and microRNA-19 regulate CTGF and TSP-1 expression in age-related heart failure. Aging Cell 2011, 10(5):769-779.
  • [27]Ohgawara T, Kubota S, Kawaki H, Kondo S, Eguchi T, Kurio N, Aoyama E, Sasaki A, Takigawa M: Regulation of chondrocytic phenotype by micro RNA 18a: involvement of Ccn2/Ctgf as a major target gene. FEBS Lett 2009, 583(6):1006-1010.
  文献评价指标  
  下载次数:21次 浏览次数:26次