Effects of arsenic trioxide and imatinib mesylate on proliferation and apoptosis in lymphoblastoid Raji cell line
10.3760/cma.j.issn.1009-9921.2010.04.005
- VernacularTitle:亚砷酸与甲磺酸伊马替尼单用及联用对淋巴瘤细胞Raji增殖和凋亡的影响
- Author:
Li MA
;
Liangming MA
- Publication Type:Journal Article
- Keywords:
Arsenic trioxide;
Imatinib mesylate;
Lymphoma;
Cell cycle;
Caspase-3;
p16
- From:
Journal of Leukemia & Lymphoma
2010;19(4):207-210,214
- CountryChina
- Language:Chinese
-
Abstract:
Objective To investigate the effect of arsenic trioxide (As2O3) and imatinib mesylate (imatinib) or in combination with imatinib with different concentration on Raji cells and the mechanisms.Methods The inhibition of cell proliferation was measured by MTT assay to assess the cells survival after As2O3 and imatinib or in combination with imatinib treatment with different concentration at indicated time.Caspase-3 activity changes and the relative number of cells in different phases and the percentages of cells calculated in G1 and S phase of the cell cycle were assessed by FCM. The expression of p16 protein was analyzed by SABC immunohistochemical method. Results The results of MTT assay showed that As2O3 and imatinib or in combination with imatinib could inhibit Raji cells growth. There was clear statistical significance between the union groups and the single-drug group (P<0.05). As2O3 inducing apoptosis was accompanied by up-regulation and activation of apoptosis protein Caspase-3. The mean percentage of apoptosis cells was both in time-and dosage-dependent form (P<0.0001). While Raji cell lines were less sensitive to imatinib than arsenic trioxide (P >0.05). Further more, Combination of imatinib with As2O3 had not a synergistic inducing apoptosis effect on Raji cells (P >0.05). The optical density of p16 protein increased both in time-and dosage-dependent form with As2O3 by immunohistochemical method (P<0.05). While at higher concentration and for a longer time, imatinib could up-regulated the optical density of p16 protein. There was no obvious statistic significance for p16 protein in Raji cells with using As2O3 only compared with the unions group(P >0.05). The cell cycle was arrested at G1 phase, the number of cells G1 period increased significantly,and S phase decreased on Raji cells after As2O3 treatment. The relationship between the cellular DNA contents and the concentration of As2O3 showed a dose-and time-dependent manner (P<0.0001). But it was found that imatinib had no effect on Raji cell cycle. There was no the obvious difference (P >0.05) between two drugs unions group with only using As2O3 group. Conclusion The results showed that As2O3 exerted variable and definite effects on lymphoma Raji cells, and suggested that As2O3 might induce apoptosis and up-regulate the optical density of p16 protein and arrest cell cycle. As for Raji cells, imatinib might affect the expression of p16 protein at higher concentration. Two drugs unions had no effective and synergistic effect.
