摘要
目的:探究川芎挥发油(LCH)通过富含亮氨酸重复序列和免疫球蛋白样结构域2(LRIG2)调控表皮生长因子受体(EGFR)/血管内皮生长因子A(VEGF-A)通路对胶质瘤血管生成的影响。方法:体外培养人恶性胶质瘤U87 MG细胞,分别采用低(L-LCH)、高(H-LCH)剂量LCH进行处理,检测LCH对U87 MG细胞恶性生物学行为(CCK-8检测增殖能力,Transwell实验检测迁移、侵袭能力)及血管生成(三维培养实验)的影响;体外培养U87 MG细胞及正常人星形胶质细胞(HA1800细胞),Western blot检测LRIG2、EGFR、VEGF-A在两者中的表达情况及L-LCH、H-LCH对LRIG2、EGFR、VEGF-A表达的影响;向U87 MG细胞转染LRIG2过表达[LRIG2(+)]质粒,检测U87 MG细胞LRIG2、EGFR、VEGF-A表达变化,以及恶性生物学行为与血管生成情况;U87 MG细胞在H-LCH处理的同时亦给予转染LRIG2(+)质粒处理,观察其恶性生物学行为与血管生成情况。结果:L-LCH、H-LCH处理后U87 MG细胞增殖率,迁移、侵袭细胞数及小管数量均减少(P<0.05);U87 MG细胞LRIG2、EGFR、 VEGF-A蛋白表达较之HA1800细胞均增加(P<0.05);L-LCH、H-LCH处理后U87 MG细胞LRIG2、EGFR、VEGF-A蛋白表达均减少(P<0.05);增加转染LRIG2(+)质粒处理可部分逆转H-LCH对U87 MG细胞增殖、迁移、侵袭和血管生成的影响。结论:LCH能抑制U87 MG细胞恶性生物学行为及血管生成,可能通过下调LRIG2表达,进而下调EGFR、VEGF-A表达而实现。
Objective: To explore the impacts of volatile oil of Ligusticum Chuanxiong(LCH) on the angiogenesis in glioma by regulating epidermal growth factor receptor(EGFR)/vascular endothelial growth factor A(VEGF-A) pathway via leucine-rich repeats and immunoglobulin-like domains(LRIG2). Methods: Human malignant glioma U87 MG cells were cultured in vitro, and treated with low and high dose of LCH(L-LCH, H-LCH), respectively. The impacts of LCH on the malignant biological behavior of U87 MG cells(proliferation ability detected by CCK-8, migration and invasion ability detected by Transwell assay) and angiogenesis(three-dimensional culture experiment) were detected. U87 MG cells and normal human astrocytes(HA1800 cells) were cultured in vitro. Western blot was used to detect the expression levels of LRIG2, EGFR and VEGF-A, and the impacts of L-LCH and H-LCH on the expression levels of LRIG2, EGFR and VEGF-A. U87 MG cells were transfected with LRIG2 overexpressing [LRIG2(+)] plasmid to detect the expression changes of LRIG2, EGFR and VEGF-A, malignant biological behavior and angiogenesis in U87 MG cells. U87 MG cells were also transfected with LRIG2(+) plasmid when treated with H-LCH, and their malignant biological behavior and angiogenesis were observed. Results: The cell proliferation rate, the numbers of migrating and invasive cells, and the number of tubules of U87 MG cells were all decreased after L-LCH and H-LCH treatment(P<0.05);the protein expression of LRIG2, EGFR and VEGF-A in U87 MG cells was increased compared with that in HA1800 cells(P<0.05);the protein expression of LRIG2, EGFR and VEGF-A in U87 MG cells was decreased after L-LCH and H-LCH treatment(P<0.05);the effects of H-LCH on U87 MG cell proliferation, migration, invasion and angiogenesis could be partially reversed by adding LRIG2(+) plasmid transfected treatment.Conclusion: LCH can inhibit the malignant biological behavior and angiogenesis of U87 MG cells, which may be achieved by down-regulating the expression of LRIG2, and then down-regulating the exp
作者
郝玉梅
李瑞斌
杨杰
周玲
Hao Yumei;Li Ruibin;Yang Jie;Zhou Ling(Department of Neurosurgery,Minmetals Hanxing Staff General Hospital,Hebei Handan 056005,China;Department of Critical Medicine,Minmetals Hanxing Staff General Hospital;Department of Traditional Chinese Medicine,HengshuiPeople's Hospital)
出处
《中国药师》
CAS
2022年第11期1873-1877,1903,共6页
China Pharmacist
基金
河北省中医药管理局科研计划项目(编号:2021194)。
