硼替佐米抑制神经胶质瘤细胞增殖及促进其凋亡的机制

Molecular Mechanism of the Bortezomib Inhibiting Growth and Promoting Apoptosis in Neuroglioma Cell Lines

目的:研究硼替佐米对神经胶质瘤细胞增殖和凋亡的影响,并对其机制进行探讨,为临床应用硼替佐米治疗神经胶质瘤提供理论依据。方法:MTT法检测硼替佐米作用于神经胶质瘤后细胞增殖情况;DAPI染色和流式细胞技术检测硼替佐米作用于神经胶质瘤后细胞凋亡情况;Western blot技术检测RAF/MEK/ERK通路中相关蛋白及凋亡相关蛋白的表达水平。结果:硼替佐米作用于神经胶质瘤细胞后,可以明显抑制胶质瘤细胞的增殖并促进其凋亡(P<0.05);在硼替佐米的作用下,胶质瘤细胞RAF/MEK/ERK通路中MEK和ERK磷酸化水平明显降低,并且凋亡抑制因子Bcl-xL和Mcl-1的表达也明显降低(P<0.05)。结论:硼替佐米对神经胶质瘤细胞可以产生抑制生长和促进凋亡的作用,提示硼替佐米作为神经胶质瘤临床化学治疗药物具有可行性。

Objective：To investigate the effect of bortezomib on the proliferation and apoptosis of neuroglioma and its mechanism for providing a theoretical basis for the clinical application of bortezomib in the treatment for neuroglioma.Methods：Cell viability of neuroglioma was analyzed by MTT after treatment with bortezomib;apoptosis of neuroglioma cells was evaluated by DAPI staining and flow cytometry;the expression levels of RAF/MEK/ERK pathway related proteins and apoptosis related proteins were detected by Western blot.Results：The proliferation of neuroglioma cells was significantly inhibited and the apoptosis was significantly promoted after treatment with bortezomib（P〈0.05）;phosphorylations of MEK and ERK in RAF/MEK/ERK pathway were significantly inhibited and the expressions of Bcl-xL and Mcl-1,which act as apoptosis inhibitor,also decreased（P〈0.05）.Conclusion：Bortezomib can inhibit the proliferation of neuroglioma cells and promote their apoptosis,suggesting that bortezomib as neuroglioma clinical chemotherapy is feasible.