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。
Objective To investigate whether Racl 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 Racl inhibitor, TMZ or Racl inhibitor combined with TMZ. They were divided into 4 groups: control group, Racl inhibitor group, TMZ group and Racl 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 Racl inhibitor, TMZ or Racl inhibitor +TMZ, the cell proliferation of U87 and U251 were inhibited (P 〈 0.05, for all). The inhibiting effect of TMZ was stronger than Rael inhibitor (P 〈 0.05, for all), while Rael inhibitor + TMZ was much stronger (P 〈 0.05, for all). U87 and U251 migration [cells/low power field (LPF)] in Racl inhibitor group (39.00 ± 9.53, 37.00 ± 5.56), TMZ group (42.00 ± 8.54, 36.00±9.00) and Racl 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 (eells/LPF) in Rael inhibitor group (30.33 ±3.51, 40.67 ± 4.04), TMZ group (24.00 ± 2.64, 37.33 ± 4.51) and Racl 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 ceils in Racl inhibitor + TMZ group were significantly decreased than those in other groups. Conclusions Both Racl inhibitor and temozolomide can inhibit the proliferation, migratio
出处
《中国现代神经疾病杂志》
CAS
2016年第8期509-515,共7页
Chinese Journal of Contemporary Neurology and Neurosurgery