Xu Y, Jiang W-G, Wang H-C, Martin T, Zeng Y-X, Zhang J, Qi Y-S
Department of Gynaecology, Zibo Maternity and Child Health Hospital, Zibo, China.
Eur Rev Med Pharmacol Sci. 2019 Jun;23(12):5093-5100. doi: 10.26355/eurrev_201906_18173.
Abnormal expression and activation of tropomyosin-related kinase receptor B (TrkB) are observed in many pathological conditions, including many types of cancer. We try to explore the relationship between ovarian cancer and Brain-derived neurotrophic factor (BDNF), a ligand of TrkB.
Human ovarian cancer cell line SKOV-3 was used in this study. qPCR, immunohistochemistry, and immunoblot were used to assay BDNF and TrkB expression level. Scratch assay was used to test the cell motility, and transwell assay was used to test the cell migration ability.
We found that BDNF promotes the proliferation and invasion of human ovarian cancer SKOV-3 cells depend on the activation of TrkB. To illuminate the downstream pathway of BDNF/TrkB, we silenced AKT1 and PLCγ1 by siRNA. The functional assay showed that activated PLCγ1 signaling pathway is necessary for the proliferation and invasion of cancer cells other than the AKT pathway. Further study showed that PLCγ1 could inhibit the apoptosis of cancer cells.
BDNF triggers TrkB/PLCγ1 signaling pathway to promote proliferation and invasion of ovarian cancer cells through inhibition of apoptosis.
在包括多种癌症在内的许多病理状况下，均观察到原肌球蛋白相关激酶受体B（TrkB）的异常表达和激活。我们试图探究卵巢癌与TrkB的配体脑源性神经营养因子（BDNF）之间的关系。
本研究采用人卵巢癌细胞系SKOV-3。运用qPCR、免疫组织化学和免疫印迹法检测BDNF和TrkB的表达水平。采用划痕试验检测细胞运动性，采用Transwell试验检测细胞迁移能力。
我们发现BDNF通过TrkB的激活促进人卵巢癌SKOV-3细胞的增殖和侵袭。为阐明BDNF/TrkB的下游通路，我们用小干扰RNA使AKT1和PLCγ1沉默。功能试验表明，除AKT通路外，激活的PLCγ1信号通路对癌细胞的增殖和侵袭是必需的。进一步研究表明，PLCγ1可抑制癌细胞凋亡。
BDNF通过抑制凋亡触发TrkB/PLCγ1信号通路，促进卵巢癌细胞的增殖和侵袭。
