Mechanism of decitabine in inhibiting cell proliferation and inducing apoptosis of AML1-ETO+ leukemia cells
- VernacularTitle:地西他滨抑制AML1-ETO+白血病细胞增殖和诱导凋亡的机制研究
- Author:
Haiying LI
1
;
Bin ZHOU
;
Li ZHANG
;
Shenmeng GAO
Author Information
1. 温州医科大学附属第一医院中心实验室
- Keywords:
Decitabine;
AML1-ETO;
Leukemia;
miR-193a
- From:
China Modern Doctor
2018;56(15):4-8
- CountryChina
- Language:Chinese
-
Abstract:
Objective To study the decitabine inhibits the proliferation and induces apoptosis of AML1-ETO+ leukemia cells and to explore its possible mechanism. Methods Kasumi-1 cells were commonly cultured in RPMI-1640 medium containing 10％ fetal bovine serum. The proliferation of Kasumi-1 cells was determined by CCK8 assay. Flow cytometry was used to detect Kasumi-1 apoptosis. Related protein expression was measured by Western Blot. The expressions of AML1-ETOand miR-193a were measured by RT-PCR. Results Decitabine could inhibit the proliferation of Kasumi-1 cells with concentration effect and time effect, and could induce apoptosis. The apoptosis rates of control group, 24 hours and 48 hours group were (5. 29±0. 88)％ and (9. 83±1. 71)％ and (19. 47±1. 84)％, respectively. Decitabine could decrease the expression of AML1-ETOprotein, and the AML1-ETOprotein ratios of 0. 1, 0. 5 and 1 μmol/Ldecitabine group to the control group were (0. 85±0. 21), (0. 28土0. 06) and (0. 10±0. 07). The ratios of AML1-ETOprotein of 24 hours group, 48 hours group to control group were (0. 31±0. 21) and (0. 24±0. 11). But decitabin did not affect the expression of AML1-ETOmRNA, and the ratios of AML1-ETOmRNAof 24 hours group and 48 hours group to control group were (0. 96±0. 19) and (0. 84±0. 11). The difference was not significant(F=1. 22, P＞0. 05). Decitabine could up-regulate the expression of miR-193a by (3. 61士0. 06) and (6. 99±0. 74) fold respectively at 24 and 48 hours, and decreased the expression of MDM2 and Cyclin Dl. The protein expression ratios of MDM2 and Cyclin D1 of dosing group and control group were (0. 51土0. 19) and (0. 50±0. 10), respectively. Conclusion Decitabine inhibits the proliferation and induces apoptosis of AML1-ETO+ leukemia cells by up-regulating miR-193a to repress the translation of AML1-ETOand inhibiting the expression of MDM2 and Cyclin Dl.
