Effects of TrkB-BDNF signal pathway on synthesis and secretion of vascular endothelial growth factor in human neuroblastoma cells

LI Kun-Xia; LI Ai-Min; ZHANG Ji-Hong

PDF(956 KB)

Chinese Journal of Contemporary Pediatrics ›› 2011, Vol. 13 ›› Issue (3) : 240-243.

Effects of TrkB-BDNF signal pathway on synthesis and secretion of vascular endothelial growth factor in human neuroblastoma cells

LI Kun-Xia, LI Ai-Min, ZHANG Ji-Hong

Author information +

History +

Abstract

OBJECTIVE: To study the effects of TrkB-BDNF signal pathway on the synthesis and secretion of vascular endothelial growth factor (VEGF) in human neuroblastoma cells (NB). METHODS: TrkB protein expression in SY5Y cells before and after all-trans-retinoicacid (ATRA) treatment was detected by Western blot. P-TrkB protein expression in SY5Y cells before and after the treatment of ATRA along with BDNF was also detected by Western blot. VEGF concentrations in the SY5Y cell culture supernatants were measured using ELISA after the treatment with ATRA, BDNF, tyrosine kinase inhibitor K252a and PI3k inhibitor LY294002. RESULTS: TrkB protein was undetectable in SY5Y cells before ATRA treatment. After the treatment of 1, 10 and 100 nM/L ATRA for five days, TrkB protein was expressed in SY5Y cells and the TrkB protein level increased with the increasing ATRA concentration. P-TrkB protein was not expressed in SY5Y cells treated only with 10 nM/L ATRA, but it was detectable after the treatment of ATRA along with BDNF. VEGF concentrations in the group treated with ATRA+BDNF were significantly higher than those in the untreated control and the ATRA alone treatment groups (P<0.01). VEGF concentrations in the K252a pretreated ATRA+BDNF group were significantly lower than those in the group treated with ATRA+BDNF (P＜0.05). VEGF concentrations in the LY294002 treatment group (ATRA+LY294002+BDNF group) were also significantly lower than those in the group treated with ATRA+BDNF (P＜0.01). CONCLUSIONS: Activation of TrkB-BDNF signal pathway may increase the synthesis and secretion of VEGF in human NB cells. The synthesis and secretion of VEGF can be inhibited by blocking TrkB-BDNF signal pathway with K252a or blocking the TrkB-BDNF downstream signal pathway PI3K/Akt with LY294002.

Key words

Neuroblastoma / TrkB-BDNF / LY294002 / Vascular endothelial growth factor / SH-SY5Y cell

Cite this article

EndNote

Ris (Procite)

Bibtex

Download Citations

LI Kun-Xia, LI Ai-Min, ZHANG Ji-Hong. Effects of TrkB-BDNF signal pathway on synthesis and secretion of vascular endothelial growth factor in human neuroblastoma cells[J]. Chinese Journal of Contemporary Pediatrics. 2011, 13(3): 240-243

References

［1］Iyer R, Evans AE, Qi X, Ho R, Minturn JE, Zhao H, et al. Lestaurtinib enhances the antitumor efficacy of chemotherapy in murine xenograft models of neuroblastoma［J］. Clin Cancer Res, 2010, 16(5): 1478-1485.

［2］张继红，张锦华，李爱敏，范莹.神经生长因子受体对神经母细胞瘤血管生成作用的研究［J］.中国当代儿科杂志，2004,6（2）：93-97.

［3］杨华强，张荣环，章正华，石楚成，夏云金.急性淋巴细胞白血病患儿血浆血管内皮生长因子及组织因子的测定及临床意义［J］.中国当代儿科杂志，2007,9（6）：526-528.

［4］Nowicki M, Konwerska A, Ostalska-Nowicka D, Derwich K, Miskowiak B, Kondraciuk B, et al.Vascular endothelial growth factor (VEGF)-C-a potent risk factor in children diagnosed with stadium 4 neuroblastoma［J］. Folia Histochem Cytobiol, 2008, 46（4）: 493-499.

［5］El-Houseini ME, Abdel-Azim SA, El-Desouky GI, Abdel-Hady S, El-Hamad MF, Kamel AM. Clinical significance of vascular endothelial growth factor (VEGF) in sera of patients with pediatric malignancies［J］. J Egypt Natl Canc Inst, 2004, 16（1）: 57-61.

［6］Jakovijevi'c G, Culi'c S, Stepan J, Bonevski A, Seiwerth S.Vascular endothelial growth factor in children with neuroblastoma: a retrospective analysis［J］. J Exp Clin Cancer Res, 2009, 28: 143.

［7］Thiele CJ, Li Z, Mckee AE. On Trk--the TrkB signal transduction pathway is an increasingly important target in cancer biology［J］. Clin Cancer Res, 2009, 15(19): 59625967.

［8］Zhu H, Zheng J, Xiao X, Zheng S, Dong K, Liu J, et al. Environmental endocrine disruptors promote invasion and metastasis of SK-N-SH human neuroblastoma cells［J］. Oncol Rep, 2010, 23(1): 129-139.

［9］Ma L, Young J, Prabhala H, Pan E, Mestdagh P, Muth D, et al. miR-9, a MYC/MYCN-activated microRNA, regulates E-cadherin and cancer metastasis［J］. Nat Cell Biol, 2010, 12(3): 247-256.

［10］Zhang J, Zheng Y, Wang Y, Tong H. The studies on the correlation for gene expression of tyrosine-kinase receptors and vascular endothelial growth factor in human neuroblastomas［J］.J Pediatr Hematol Oncol, 2010, 32(3): 180-184.

［11］Morotti A, Mila S, Accornero P, Tagliabue E, Ponzetto C. K252a inhibits the oncogenic properties of Met, the HGF receptor［J］.Oncogene, 2002, 25, 21(32): 4885-4893.

［12］Roux PP, Dorval G, Boudreau M, Angers-Loustau A, Morris SJ, Makkerh J, et al. K252a and CEP1347 are neuroprotective compounds that inhibit mixed-lineage kinase-3 and induce activation of Akt and ERK［J］. J Biol Chem, 2002, 277(51): 49473-49480.

［13］Dey JH, Bianchi F,Voshol J, Bonenfant D, Oakeley EJ, Hynes NE. Targeting fibroblast growth factor receptors blocks PI3K/AKT signaling, induces apoptosis, and impairs mammary tumor outgrowth and metastasis［J］. J Cancer Res, 2010, 70（10）: 4151-4162.