Objective: To study the function and potential mechanism of RAC1 inhibitors in NF2-associated schwannoma. Methods: In this study, we the downregulation of RAC1 activity and tumor cell phenotypes by RAC1 inhibitor NSC23766 in vitro. And we further validated the anti-proliferation effect by this RAC1 inhibitor in subcutaneous xenograft tumor model and sciatic nerve model. Results: Pharmacological inhibition of RAC1 could significantly inhibit the proliferation of both RT4 cells and human NF2-associated primary schwannoma cells by inducing apoptosis. Pharmacological inhibition of RAC1 effectively reduced Rac1 activity and down-regulated the pathway downstream of Rac. Moreover, pharmacological inhibition of RAC1 showed a potential antitumor effect, with low toxicity in vivo. Conclusion: RAC1 inhibitors may play a therapeutic role in patients with schwannoma.
基金:
National Natural Science Foundation of ChinaNational Natural Science Foundation of China [81372715, 81502453]; Natural Science Foundation of BeijingBeijing Natural Science Foundation [7162057]; Youth Foundation of the Beijing neurosurgical institute [2014-13]
第一作者机构:[1]Capital Med Univ, Beijing Neurosurg Inst, Beijing, Peoples R China;
通讯作者:
通讯机构:[1]Capital Med Univ, Beijing Neurosurg Inst, Beijing, Peoples R China;[2]Capital Med Univ, Beijing Tiantan Hosp, Dept Neurosurg, Beijing, Peoples R China
推荐引用方式(GB/T 7714):
Wang Ying,Wang Bo,Li Peng,et al.Reduced RAC1 activity inhibits cell proliferation and induces apoptosis in neurofibromatosis type 2(NF2)-associated schwannoma[J].NEUROLOGICAL RESEARCH.2017,39(12):1086-1093.doi:10.1080/01616412.2017.1376494.
APA:
Wang, Ying,Wang, Bo,Li, Peng,Zhang, Qi&Liu, Pinan.(2017).Reduced RAC1 activity inhibits cell proliferation and induces apoptosis in neurofibromatosis type 2(NF2)-associated schwannoma.NEUROLOGICAL RESEARCH,39,(12)
MLA:
Wang, Ying,et al."Reduced RAC1 activity inhibits cell proliferation and induces apoptosis in neurofibromatosis type 2(NF2)-associated schwannoma".NEUROLOGICAL RESEARCH 39..12(2017):1086-1093