Skip to main content
Erschienen in: Tumor Biology 12/2016

29.07.2015 | Research Article

RETRACTED ARTICLE: Ginsenoside Rh2 inhibits invasiveness of glioblastoma through modulation of VEGF-A

verfasst von: Shaoyi Li, Yun Gao, Weining Ma, Tianci Cheng, Yunhui Liu

Erschienen in: Tumor Biology | Ausgabe 12/2016

Einloggen, um Zugang zu erhalten

Abstract

The malignancy of glioblastoma multiforme (GBM) is largely due to its local invasion and the presence of the tumor in the relatively restrained region in the brain. Hence, effective prevention of the cancer cell invasion is substantially critical for controlling the growth and deterioration of GBM. We have recently reported the role of ginsenoside Rh2 (GRh2) in suppressing the growth of GBM through EGFR/PI3k/Akt/mTor signaling pathways. Here, we further showed that GRh2 efficiently inhibited the cancer vascularization in vivo. In vitro, GRh2 dose-dependently inhibited the protein, but not messenger RNA (mRNA) of vascular endothelial growth factor A (VEGF-A) in GBM cells. We then examined the underlying mechanisms and found that GRh2 increased the levels of miR-497, which bound to 3′UTR of VEGF-A mRNA to inhibit its translation. Together, our data demonstrate a previously unappreciated role for GRh2 in inhibition of GBM-associated cancer vascularization, which may contribute to the effects of GRh2 on suppression of GBM cancer growth and invasion.
Literatur
1.
Zurück zum Zitat Chen J, Huang Q, Wang F. Inhibition of foxo1 nuclear exclusion prevents metastasis of glioblastoma. Tumour Biol. 2014;35:7195–200.CrossRefPubMed Chen J, Huang Q, Wang F. Inhibition of foxo1 nuclear exclusion prevents metastasis of glioblastoma. Tumour Biol. 2014;35:7195–200.CrossRefPubMed
2.
Zurück zum Zitat Wang F, Xiao W, Sun J, Han D, Zhu Y. Mirna-181c inhibits egfr-signaling-dependent mmp9 activation via suppressing akt phosphorylation in glioblastoma. Tumour Biol. 2014;35:8653–8.CrossRefPubMed Wang F, Xiao W, Sun J, Han D, Zhu Y. Mirna-181c inhibits egfr-signaling-dependent mmp9 activation via suppressing akt phosphorylation in glioblastoma. Tumour Biol. 2014;35:8653–8.CrossRefPubMed
3.
Zurück zum Zitat Yu Y, Ran Q. Nuclear smad2 restrains proliferation of glioblastoma. Cell Physiol Biochem. 2015;35:1756–63.CrossRefPubMed Yu Y, Ran Q. Nuclear smad2 restrains proliferation of glioblastoma. Cell Physiol Biochem. 2015;35:1756–63.CrossRefPubMed
4.
Zurück zum Zitat Gong J, Zhu S, Zhang Y, Wang J. Interplay of vegfa and mmp2 regulates invasion of glioblastoma. Tumour Biol. 2014;35:11879–85.CrossRefPubMed Gong J, Zhu S, Zhang Y, Wang J. Interplay of vegfa and mmp2 regulates invasion of glioblastoma. Tumour Biol. 2014;35:11879–85.CrossRefPubMed
5.
Zurück zum Zitat Yu X, Jiang Y, Wei W, Cong P, Ding Y, Xiang L, et al. Androgen receptor signaling regulates growth of glioblastoma multiforme in men. Tumour Biol. 2015;36:967–72.CrossRefPubMed Yu X, Jiang Y, Wei W, Cong P, Ding Y, Xiang L, et al. Androgen receptor signaling regulates growth of glioblastoma multiforme in men. Tumour Biol. 2015;36:967–72.CrossRefPubMed
8.
Zurück zum Zitat Ferrara N, Gerber HP, LeCouter J. The biology of vegf and its receptors. Nat Med. 2003;9:669–76.CrossRefPubMed Ferrara N, Gerber HP, LeCouter J. The biology of vegf and its receptors. Nat Med. 2003;9:669–76.CrossRefPubMed
9.
Zurück zum Zitat Xiao X, Prasadan K, Guo P, El-Gohary Y, Fischbach S, Wiersch J, et al. Pancreatic duct cells as a source of vegf in mice. Diabetologia. 2014;57:991–1000.CrossRefPubMedPubMedCentral Xiao X, Prasadan K, Guo P, El-Gohary Y, Fischbach S, Wiersch J, et al. Pancreatic duct cells as a source of vegf in mice. Diabetologia. 2014;57:991–1000.CrossRefPubMedPubMedCentral
10.
Zurück zum Zitat Xiao X, Guo P, Chen Z, El-Gohary Y, Wiersch J, Gaffar I, et al. Hypoglycemia reduces vascular endothelial growth factor a production by pancreatic beta cells as a regulator of beta cell mass. J Biol Chem. 2013;288:8636–46.CrossRefPubMedPubMedCentral Xiao X, Guo P, Chen Z, El-Gohary Y, Wiersch J, Gaffar I, et al. Hypoglycemia reduces vascular endothelial growth factor a production by pancreatic beta cells as a regulator of beta cell mass. J Biol Chem. 2013;288:8636–46.CrossRefPubMedPubMedCentral
11.
Zurück zum Zitat Ye H, Wu Q, Zhu Y, Guo C, Zheng X. Ginsenoside rh2 alleviates dextran sulfate sodium-induced colitis via augmenting tgfbeta signaling. Mol Biol Rep. 2014;41:5485–90.CrossRefPubMed Ye H, Wu Q, Zhu Y, Guo C, Zheng X. Ginsenoside rh2 alleviates dextran sulfate sodium-induced colitis via augmenting tgfbeta signaling. Mol Biol Rep. 2014;41:5485–90.CrossRefPubMed
12.
Zurück zum Zitat Kikuchi Y, Sasa H, Kita T, Hirata J, Tode T, Nagata I. Inhibition of human ovarian cancer cell proliferation in vitro by ginsenoside rh2 and adjuvant effects to cisplatin in vivo. Anti-Cancer Drugs. 1991;2:63–7.CrossRefPubMed Kikuchi Y, Sasa H, Kita T, Hirata J, Tode T, Nagata I. Inhibition of human ovarian cancer cell proliferation in vitro by ginsenoside rh2 and adjuvant effects to cisplatin in vivo. Anti-Cancer Drugs. 1991;2:63–7.CrossRefPubMed
13.
Zurück zum Zitat Tode T, Kikuchi Y, Hirata J, Kita T, Imaizumi E. Nagata I: [inhibitory effects of oral administration of ginsenoside rh2 on tumor growth in nude mice bearing serous cyst adenocarcinoma of the human ovary]. Nihon Sanka Fujinka Gakkai zasshi. 1993;45:1275–82.PubMed Tode T, Kikuchi Y, Hirata J, Kita T, Imaizumi E. Nagata I: [inhibitory effects of oral administration of ginsenoside rh2 on tumor growth in nude mice bearing serous cyst adenocarcinoma of the human ovary]. Nihon Sanka Fujinka Gakkai zasshi. 1993;45:1275–82.PubMed
14.
Zurück zum Zitat Tode T, Kikuchi Y, Kita T, Hirata J, Imaizumi E, Nagata I. Inhibitory effects by oral administration of ginsenoside rh2 on the growth of human ovarian cancer cells in nude mice. J Cancer Res Clin Oncol. 1993;120:24–6.CrossRefPubMed Tode T, Kikuchi Y, Kita T, Hirata J, Imaizumi E, Nagata I. Inhibitory effects by oral administration of ginsenoside rh2 on the growth of human ovarian cancer cells in nude mice. J Cancer Res Clin Oncol. 1993;120:24–6.CrossRefPubMed
15.
Zurück zum Zitat Nakata H, Kikuchi Y, Tode T, Hirata J, Kita T, Ishii K, et al. Inhibitory effects of ginsenoside rh2 on tumor growth in nude mice bearing human ovarian cancer cells. Jpn J Cancer Res. 1998;89:733–40.CrossRefPubMed Nakata H, Kikuchi Y, Tode T, Hirata J, Kita T, Ishii K, et al. Inhibitory effects of ginsenoside rh2 on tumor growth in nude mice bearing human ovarian cancer cells. Jpn J Cancer Res. 1998;89:733–40.CrossRefPubMed
16.
Zurück zum Zitat Tang XP, Tang GD, Fang CY, Liang ZH, Zhang LY. Effects of ginsenoside rh2 on growth and migration of pancreatic cancer cells. World J Gastroenterol. 2013;19:1582–92.CrossRefPubMedPubMedCentral Tang XP, Tang GD, Fang CY, Liang ZH, Zhang LY. Effects of ginsenoside rh2 on growth and migration of pancreatic cancer cells. World J Gastroenterol. 2013;19:1582–92.CrossRefPubMedPubMedCentral
17.
Zurück zum Zitat Liu J, Shimizu K, Yu H, Zhang C, Jin F, Kondo R. Stereospecificity of hydroxyl group at c-20 in antiproliferative action of ginsenoside rh2 on prostate cancer cells. Fitoterapia. 2010;81:902–5.CrossRefPubMed Liu J, Shimizu K, Yu H, Zhang C, Jin F, Kondo R. Stereospecificity of hydroxyl group at c-20 in antiproliferative action of ginsenoside rh2 on prostate cancer cells. Fitoterapia. 2010;81:902–5.CrossRefPubMed
18.
Zurück zum Zitat Li B, Zhao J, Wang CZ, Searle J, He TC, Yuan CS, et al. Ginsenoside rh2 induces apoptosis and paraptosis-like cell death in colorectal cancer cells through activation of p53. Cancer Lett. 2011;301:185–92.CrossRefPubMed Li B, Zhao J, Wang CZ, Searle J, He TC, Yuan CS, et al. Ginsenoside rh2 induces apoptosis and paraptosis-like cell death in colorectal cancer cells through activation of p53. Cancer Lett. 2011;301:185–92.CrossRefPubMed
19.
Zurück zum Zitat Oh M, Choi YH, Choi S, Chung H, Kim K, Kim SI, et al. Anti-proliferating effects of ginsenoside rh2 on mcf-7 human breast cancer cells. Int J Oncol. 1999;14:869–75.PubMed Oh M, Choi YH, Choi S, Chung H, Kim K, Kim SI, et al. Anti-proliferating effects of ginsenoside rh2 on mcf-7 human breast cancer cells. Int J Oncol. 1999;14:869–75.PubMed
20.
Zurück zum Zitat Choi S, Kim TW, Singh SV. Ginsenoside rh2-mediated g1 phase cell cycle arrest in human breast cancer cells is caused by p15 ink4b and p27 kip1-dependent inhibition of cyclin-dependent kinases. Pharm Res. 2009;26:2280–8.CrossRefPubMedPubMedCentral Choi S, Kim TW, Singh SV. Ginsenoside rh2-mediated g1 phase cell cycle arrest in human breast cancer cells is caused by p15 ink4b and p27 kip1-dependent inhibition of cyclin-dependent kinases. Pharm Res. 2009;26:2280–8.CrossRefPubMedPubMedCentral
21.
Zurück zum Zitat Li S, Gao Y, Ma W, Guo W, Zhou G, Cheng T, et al. Egfr signaling-dependent inhibition of glioblastoma growth by ginsenoside rh2. Tumour Biol. 2014;35:5593–8.CrossRefPubMed Li S, Gao Y, Ma W, Guo W, Zhou G, Cheng T, et al. Egfr signaling-dependent inhibition of glioblastoma growth by ginsenoside rh2. Tumour Biol. 2014;35:5593–8.CrossRefPubMed
22.
Zurück zum Zitat Li S, Guo W, Gao Y, Liu Y. Ginsenoside rh2 inhibits growth of glioblastoma multiforme through mtor. Tumour Biol. 2015;36:2607–12.CrossRefPubMed Li S, Guo W, Gao Y, Liu Y. Ginsenoside rh2 inhibits growth of glioblastoma multiforme through mtor. Tumour Biol. 2015;36:2607–12.CrossRefPubMed
23.
Zurück zum Zitat Giard DJ, Aaronson SA, Todaro GJ, Arnstein P, Kersey JH, Dosik H, et al. In vitro cultivation of human tumors: Establishment of cell lines derived from a series of solid tumors. J Natl Cancer Inst. 1973;51:1417–23.CrossRefPubMed Giard DJ, Aaronson SA, Todaro GJ, Arnstein P, Kersey JH, Dosik H, et al. In vitro cultivation of human tumors: Establishment of cell lines derived from a series of solid tumors. J Natl Cancer Inst. 1973;51:1417–23.CrossRefPubMed
Metadaten
Titel
RETRACTED ARTICLE: Ginsenoside Rh2 inhibits invasiveness of glioblastoma through modulation of VEGF-A
verfasst von
Shaoyi Li
Yun Gao
Weining Ma
Tianci Cheng
Yunhui Liu
Publikationsdatum
29.07.2015
Verlag
Springer Netherlands
Erschienen in
Tumor Biology / Ausgabe 12/2016
Print ISSN: 1010-4283
Elektronische ISSN: 1423-0380
DOI
https://doi.org/10.1007/s13277-015-3759-6

Weitere Artikel der Ausgabe 12/2016

Tumor Biology 12/2016 Zur Ausgabe

Update Onkologie

Bestellen Sie unseren Fach-Newsletter und bleiben Sie gut informiert.