Study on synergistic effect of Rac1 inhibitor and temozolomide in inhibiting proliferation and invasiveness of glioma cells in vitro

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.

DOI: 10.3969/j.issn.1672-6731.2016.08.009