Abstract:

Objective  To investigate whether Rac1 inhibitor has a synergistic effect on temozolomide (TMZ) in inhibiting the proliferation, migration and invasiveness of glioma cells.  Methods  Human glioma cell lines U87 and U251 were cultured by Rac1 inhibitor, TMZ or Rac1 inhibitor combined with TMZ. They were divided into 4 groups: control group, Rac1 inhibitor group, TMZ group and Rac1 inhibitor + TMZ group. The proliferation, migration and invasiveness of glioma cells were detected by methyl thiazolyl tetrazolium (MTT), migration assay and Transwell assay.  Results  After cultured by Rac1 inhibitor, TMZ or Rac1 inhibitor + TMZ, the cell proliferation of U87 and U251 were inhibited (P < 0.05, for all). The inhibiting effect of TMZ was stronger than Rac1 inhibitor (P < 0.05, for all), while Rac1 inhibitor + TMZ was much stronger (P < 0.05, for all). U87 and U251 migration [cells/low power field (LPF)] in Rac1 inhibitor group (39.00 ± 9.53, 37.00 ± 5.56), TMZ group (42.00 ± 8.54, 36.00 ± 9.00) and Rac1 inhibitor + TMZ group (18.67 ± 10.54, 14.33 ± 5.00) was lower than that in control group (78.00 ± 11.53, 75.00 ± 4.00), and the differences were significant (U87: P = 0.001, 0.001, 0.000; U251: P = 0.000, for all). U87 and U251 cell invasiveness (cells/LPF) in Rac1 inhibitor group (30.33 ± 3.51, 40.67 ± 4.04), TMZ group (24.00 ± 2.64, 37.33 ± 4.51) and Rac1 inhibtor + TMZ group (11.00 ± 2.00, 15.33 ± 2.52) was lower than that in control group (64.33 ± 4.04, 77.33 ± 3.06), and the differences were significant (U87: P = 0.000, for all; U251: P = 0.000, for all). In paired comparison among different groups, the migration (U87: P = 0.021, 0.011; U251: P = 0.002, 0.003) and invasiveness (U87: P = 0.000, 0.001; U251: P = 0.000, 0.000) of cells in Rac1 inhibitor + TMZ group were significantly decreased than those in other groups.  Conclusions  Both Rac1 inhibitor and temozolomide can inhibit the proliferation, migration and invasiveness of glioma cells, while Rac1 inhibitor has a significantly synergistic effect on temozolomide.

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摘要：

目的 探讨Rac1 抑制剂联合替莫唑胺对胶质瘤细胞增殖活性、迁移能力和侵袭能力的协同抑制作用。方法 分别以Rac1 抑制剂、替莫唑胺、Rac1 抑制剂联合替莫唑胺于体外培养人胶质瘤细胞系U87 和U251，噻唑蓝法、细胞迁移实验和细胞侵袭实验检测胶质瘤细胞增殖活性、迁移能力和侵袭能力。结果 经Rac1 抑制剂、替莫唑胺、Rac1 抑制剂联合替莫唑胺培养后，U87 和U251 细胞增殖活性均降低（均P < 0.05），且替莫唑胺的抑制作用强于Rac1 抑制剂（均P < 0.05），Rac1 抑制剂联合替莫唑胺的抑制作用更强（均P < 0.05）；U87 和U251 细胞迁移能力［U87：空白对照（78.00 ± 11.53）细胞数/低倍视野、Rac1 抑制剂（39.00 ± 9.53）细胞数/低倍视野、替莫唑胺（42.00 ± 8.54）细胞数/低倍视野、Rac1 抑制剂联合替莫唑胺（18.67 ± 10.54）细胞数/低倍视野，P = 0.001，0.001，0.000；U251：空白对照（75.00 ± 4.00）细胞数/低倍视野、Rac1 抑制剂（37.00 ± 5.56）细胞数/低倍视野、替莫唑胺（36.00 ± 9.00）细胞数/低倍视野、Rac1 抑制剂联合替莫唑胺（14.33 ± 5.50）细胞数/低倍视野，均P = 0.000］和侵袭能力［U87：空白对照（64.33 ± 4.04）细胞数/低倍视野、Rac1 抑制剂（30.33 ± 3.51）细胞数/低倍视野、替莫唑胺（24.00 ± 2.64）细胞数/低倍视野、Rac1 抑制剂联合替莫唑胺（11.00 ± 2.00）细胞数/低倍视野，均P = 0.000；U251：空白对照（77.33 ± 3.06）细胞数/低倍视野、Rac1 抑制剂（40.67 ± 4.04）细胞数/低倍视野、替莫唑胺（37.33 ± 4.51）细胞数/低倍视野、Rac1 抑制剂联合替莫唑胺（15.33 ± 2.52）细胞数/低倍视野，均P = 0.000］均降低，尤以二者联合应用降低更明显（迁移能力U87：P = 0.021，0.011；迁移能力U251：P = 0.002，0.003；侵袭能力U87：P =0.000，0.001；侵袭能力U251：均P = 0.000）。结论 Rac1 抑制剂和替莫唑胺均可抑制胶质瘤细胞的增殖活性、迁移能力和侵袭能力，二者联合应用更具协同抑制作用。

关键词: 神经胶质瘤, rac1 GTP 结合蛋白质, 替莫唑胺（非MeSH 词）, 细胞增殖, 肿瘤侵润, 肿瘤细胞, 培养的