蛋白激酶抑制剂Go6976增强慢性髓系白血病细胞对三氧化二砷化疗敏感性的研究

研究Go6976是否能去除As2O3引起的G2/M周期阻滞,增加慢性髓系白血病(CML)细胞株(K562细胞)对As2O3的敏感性.K562细胞经不同浓度的Go6976及和As2O3(5μmol/L)作用后,流式细胞术检测细胞周期,台盼蓝排斥试验检测细胞活力,四唑盐(MTT)比色试验分析细胞的生长增殖.结果表明,流式细胞术细胞周期检测发现K562细胞经As2O3作用24小时和48小时后,G2/M期细胞比例分别为(38.02±7.70)%和(32.58±7.43)%,未出现明显凋亡;50nmol/LGo6976与As2O3联合作用后,G2/M期细胞分别减少至(23.24±2.93)%和(16.18±1.60)%,subG1期细胞分别增加至(11.82±2.31)%和(27.80±2.89)%;且其变化随Go6976浓度及作用时间而增加.同时台盼蓝排斥试验及MTT试验观察到Go6976与As2O3联合作用能明显降低细胞活力、抑制其生长,但Go6976本身无明显作用.结论Go6976可能通过去除G2/M期阻滞,有效增强了K562细胞对As2O3化疗的敏感性.

Protein Kinase C Inhibitor Go6976 Sensitizes Arsenic Trioxide-Induced Cell Apoptosis in Chronic Myeloid Leukemic Cells

To investigate the As(2)O(3)-chemosensitization of G?6976 in K562 cells by its abrogation of As(2)O(3)-induced G(2)/M cell cycle arrest, K562 cells were treated with As(2)O(3) (5 micromol/L) and G?6976 with various concentrations, the distributions of cell cycles were detected by flow cytometry, the cell viability was observed by trypan blue exclusion test and cell proliferation was tested by MTT assay. The results indicated that having treated by As(2)O(3) for 24 h and 48 h, the proportion of K562 cells in G(2)/M phase were (38.02 +/- 7.70)% and (32.58 +/- 7.43)% respectively, and no obvious cell apoptosis appeared. 50 nmol/L G?6976 combined with As(2)O(3) decrease the proportion of cells in G(2)/M phase to (23.24 +/- 2.93)% and (16.18 +/- 1.60)% respectively and increase the proportion of cells in subG(1) phase to (11.82 +/- 2.31)% and (27.80 +/- 2.89)% respectively. G?6976 abrogated G(2)/M cell cycle arrest induced by As(2)O(3) and increased cell apoptosis in a concentration- and time-dependent manner. Additionally, comparing to the control group, G?6976 combined with As(2)O(3) decreased the cell viability and depressed the cell proliferation, but G?6976 alone showed no same effect on them. In conclusion, the effects of AS(2)O(3)-chemosensitization of G?6976 on K562 cells is associated with its abrogation of As(2)O(3)-induced G(2)/M cell cycle arrest.