TrkB受体的激活在神经母细胞瘤化疗耐药机制中作用的探讨

The Effects of Activation of TrkB on the Chemotherapy Resistance in Neuroblastoma

  • 摘要: 目的:探讨TrKB受体在神经母细胞瘤(NB)化疗耐药机制中的作用。方法:选择缺乏TrkB及BDNF表达的人类NB细胞株SH-SY5Y,应用全反式维甲酸(ATRA)诱导TrkB表达,用脑源性神经生长因子(BDNF)激活TrkB受体通路,通过四甲基偶氮蓝比色(MTT)法及流式细胞仪(FCM)检测TrkB受体激活后顺铂对SY5Y生长及凋亡的影响。结果:BDNF+顺铂组、ATRA+顺铂组细胞存活率同单用顺铂组比较均无显著差异(P>0.05);ATRA+BDNF+顺铂组(浓度2.5~20μg/ml)NB细胞存活率明显高于顺铂组(P<0.01);ATRA+BDNF+顺铂组(5μg/ml)凋亡率明显低于ATRA+顺铂组(5μg/ml)(P<0.01)。结论:TrkB受体激活可阻断顺铂对SY5Y细胞的杀伤作用,其阻断作用是通过抑制细胞凋亡而实现的。TrkB激活在NB的化疗耐药机制中可能起重要作用。

     

    Abstract: Objective :To explore the effects of activation of TrkB on the chemotherapy resistance in neurobiastoma. Methods :The lack of human NB cell line SH-SY5Y expression of TrkB and BDNF were chosen,the expression of TrkB induced by ATRA was applied;activated the TrkB with BDNF and detected the survival and apoptosis rate of the different concentration cisplatins on the human NB cell line SH-SY5Y before and after the activation of TrkB with ATT and FCM. Results :There was no significant difference in survival rates of SH-SY5Y cells between BDNF+cisplatin and cisplatin alone (P>0.05) and no significant difference between ATRA+cisplatin and cisplatin alone (P>0.05),too. The survival rate of SY5Y cells in the groups of ATRA+BDNF+cisplatin (2.5~20ug/ml)was significantly higher than in the group with cisplatin alone (P<0.01);The apoptosis rate in the group of ATRA+BDNF+cisplatin was significantly lower than in the group of ATRA+cisplatin (P<0.01). Conclusions :The activation of TrkB can block the antitumor effect of cisplatin based on its inhibiting apoptosis of SH-SY5Y and may play an important role in madiating chemotherapy resistance in NB cell.

     

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