PMID- 17044982
OWN - NLM
STAT- MEDLINE
DCOM- 20100726
LR  - 20161124
IS  - 0578-1310 (Print)
IS  - 0578-1310 (Linking)
VI  - 44
IP  - 7
DP  - 2006 Jul
TI  - [Effects of tyrosine kinase receptor B and brain-derived neurotrophic factor on 
      chemoresistance in neuroblastoma].
PG  - 535-9
AB  - OBJECTIVE: Neuroblastoma (NB) is a pediatric solid tumor derived from neural 
      crest precursor cells. It is resistant to current therapeutic protocols, 
      including high dose chemotherapy. The mechanisms of chemoresistance are very 
      complex. The recent studies have shown that the levels of tyrosine kinase 
      receptor B (TrkB) and brain-derived neurotrophic factor (BDNF) are high in NB 
      tumors with poor prognosis. The aim of this research was to explore the effects 
      of TrkB and BDNF levels on the chemotherapeutic sensitivity in neuroblastoma by 
      using the NB cell line SH-SY5Y in vitro. METHODS: The expression of TrkB protein 
      was detected with Western-blot after the treatment with different concentrations 
      of all trans-retinoic acid (ATRA). Cell survival rate was analyzed using MTT. 
      Apoptosis was detected using flow cytometry (FCM) and a transmission electron 
      microscope (TEM). RESULTS: (1) The expression of TrkB protein was undetectable in 
      SY5Y. It was positive, however, after the treatment with ATRA (1, 10, 100 nmol/L) 
      for five days. The level of TrkB protein was increased with adding of ATRA at 
      different concentrations. (2) The difference of the survival and apoptotic rate 
      between the BDNF (10 ng/ml) + ATRA (10 nmol/L) + cisplatin (CP, 5 microg/ml) 
      group (survival rate 46.51% +/- 13.44%, apoptosis rate 11.79% +/- 1.53%) and the 
      CP alone group (survival rate 38.51% +/- 9.66%, apoptosis rate 14.95% +/- 2.06%) 
      was not statistically significant (P > 0.05). The survival rate of the BDNF (50 
      ng/ml and 100 ng/ml) + ATRA (10 nmol/L) + CP (5 microg/ml) group (66.85% +/- 
      18.39%, 94.30% +/- 10.71%) was greatly higher than CP alone group (P < 0.05, P < 
      0.01), whereas the apoptotic rate (9.36% +/- 1.03%, 5.20% +/- 1.99%) was 
      significantly lower than that of the CP alone group (P < 0.01, P < 0.01). The 
      survival rates of BDNF (100 ng/ml) + ATRA (10 nmol/L) + CP (5 microg/ml) group 
      were higher than those of BDNF (50 ng/ml) + ATRA (10 nmol/L) + CP (5 microg/ml) 
      group (P < 0.01), whereas the apoptotic rates were lower than those of BDNF (50 
      ng/ml) + ATRA (10 nmol/L) + CP (5 microg/ml) group (P < 0.05). There were no 
      significant difference between the ATRA (1 nmol/L) + BDNF (50 ng/ml) + CP group 
      (survival rate 45.33% +/- 11.83%, apoptosis rate 12.48% +/- 2.48%) and the CP 
      alone group in the survival and apoptotic rates (P > 0.05). The survival rates of 
      the ATRA (10 nmol/L, 100 nmol/L) + BDNF (50 ng/ml) + CP (61.62% +/- 18.53%, 
      105.02% +/- 5.55%) group were greatly higher than those of the CP alone group (P 
      < 0.05, P < 0.01), whereas the apoptotic rate (9.36% +/- 1.03%, 5.05% +/- 1.88%) 
      was significantly lower than that of the CDDP alone group (P < 0.05, P < 0.01). 
      The survival rates of the ATRA (100 nmol/L) + BDNF (50 ng/ml) + CP group were 
      higher than those of the ATRA (10 nmol/L) + BDNF (50 ng/ml) + CP group (P < 
      0.01), whereas the apoptotic rates were lower than the ATRA (10 nmol/L) + BDNF 
      (50 ng/ml) + CP group (P < 0.01). (3) Some of the cells showed apoptotic changes 
      in the CP alone group, whereas the intranuclear chromoplasma was 
      well-distributed, the nuclear membrane was clear, and mitochondria, ribosome and 
      solvent were present in the ATRA (10 nmol/L) + BDNF (50 ng/ml) + CP group. 
      CONCLUSIONS: The sensitivity of SY5Y to CP was affected by TrkB and BDNF. The 
      higher the level of TrkB and BDNF was, the lower the sensitivity of SY5Y to CP.
FAU - Li, Ai-min
AU  - Li AM
AD  - Department of Hematology, The Second Affiliated Hospital of China Medical 
      University, Shenyang 110004, China.
FAU - Zhang, Ji-hong
AU  - Zhang JH
FAU - Zhang, Jin-hua
AU  - Zhang JH
FAU - Zhang, Ke-ren
AU  - Zhang KR
FAU - Rong, Dao-jian
AU  - Rong DJ
LA  - chi
PT  - Comparative Study
PT  - Journal Article
PL  - China
TA  - Zhonghua Er Ke Za Zhi
JT  - Zhonghua er ke za zhi = Chinese journal of pediatrics
JID - 0417427
RN  - 0 (Antineoplastic Agents)
RN  - 0 (Brain-Derived Neurotrophic Factor)
RN  - 0 (Tetrazolium Salts)
RN  - 0 (Thiazoles)
RN  - 5688UTC01R (Tretinoin)
RN  - EC 2.7.10.1 (Receptor, trkB)
RN  - EUY85H477I (thiazolyl blue)
RN  - Q20Q21Q62J (Cisplatin)
SB  - IM
MH  - Antineoplastic Agents/administration & dosage/*pharmacology
MH  - Apoptosis/drug effects
MH  - Blotting, Western
MH  - Brain-Derived Neurotrophic Factor/administration & dosage/*pharmacology
MH  - Cell Line, Tumor
MH  - Cell Survival/drug effects
MH  - Cisplatin/administration & dosage/pharmacology
MH  - Dose-Response Relationship, Drug
MH  - *Drug Resistance, Neoplasm/drug effects
MH  - Flow Cytometry
MH  - Humans
MH  - Microscopy, Electron, Transmission
MH  - Neuroblastoma/*drug therapy/*metabolism/pathology/ultrastructure
MH  - Receptor, trkB/*metabolism
MH  - Tetrazolium Salts/chemistry
MH  - Thiazoles/chemistry
MH  - Tretinoin/administration & dosage/*pharmacology
EDAT- 2006/10/19 09:00
MHDA- 2010/07/27 06:00
CRDT- 2006/10/19 09:00
PHST- 2006/10/19 09:00 [pubmed]
PHST- 2010/07/27 06:00 [medline]
PHST- 2006/10/19 09:00 [entrez]
PST - ppublish
SO  - Zhonghua Er Ke Za Zhi. 2006 Jul;44(7):535-9.