Efficacy of Quercetin-sensitized Adriamycin for Treatment of Refractory Acute Leukemia.
10.19746/j.cnki.issn.1009-2137.2019.04.017
- Author:
Ying-Xu SHI
1
;
Hua DU
2
;
Xiao-Tian SU
3
;
Yan-Qiu HAN
4
Author Information
1. Department of Clinical Laboratory, The Affiliated Hospital of Inner Mongolia Medical University，Hohhot 010030，Inner Mongolia Autonomous Region, China.
2. Department of Pathology, The Affiliated Hospital of Inner Mongolia Medical University，Hohhot 010030，Inner Mongolia Autonomous Region, China.
3. Department of Hematology, The Affiliated Hospital of Inner Mongolia Medical University，Hohhot 010030，Inner Mongolia Autonomous Region, China.
4. Department of Clinical Laboratory, The Affiliated Hospital of Inner Mongolia Medical University，Hohhot 010030，Inner Mongolia Autonomous Region, China,Department of Hematology, The Affiliated Hospital of Inner Mongolia Medical University，Hohhot 010030，Inner Mongolia Autonomous Region, China,E-mail:qyh1016@sina.com.
- Publication Type:Journal Article
- MeSH:
Animals;
Apoptosis;
Cell Proliferation;
Doxorubicin;
Humans;
Leukemia, Myeloid, Acute;
Mice;
Quercetin
- From:
Journal of Experimental Hematology
2019;27(4):1094-1103
- CountryChina
- Language:Chinese
-
Abstract:
OBJECTIVE:To investigate the chemotherapeutic efficency of quercetin sensitized adriamycin.
METHOD:CCK-8 was used to detect the inhibitory effect of different doses of adriamycin, quercetin and quercetin combined with adriamycin on the proliferation of primary leukemia cells from patients with clinically refractory acute leukemia. Quercetin, adriamycin and their combination were used to treat non-irradiated T-ALL leukemia mice to observe the changes of survival curve and myocardial injury.
RESULT:There was no significant difference in the inhibition rate of primary leukemia cell proliferation between the adriamycin concentration group (6, 0.6 and 0.06 μg/ml) and the adriamycin half-dose (3, 0.3 and 0.03 μg/ml) plus quercetin (0.25 mmol/L) group at three different time points (24, 48 and 72 hours). There was a significant difference in the inhibition rate of primary leukemia cell proliferation among the drug concentration groups, and the inhibition rate of primary leukemia cell proliferation was time-and concentration-dependent (r=0.995、r=1.000、r=0.984、r=0.993、r=0.999、r=0.960). In vivo experiments showed that the survival time of non-irradiated T-ALL leukemia mice treated with low-dose adriamycin combined with quercetin was not significantly prolonged compared with the high-dose adriamycin treatment group. The survival time of non-irradiated T-ALL leukemia mice treated with high dose of adriamycin and quercetin was significantly prolonged (P＜0.05). Compared with adriamycin group, the SOD activity in adriamycin combined with quercetin group increased significantly and the MDA content decreased. The results of transcriptome sequencing analysis showed that the expression of Ighv1-84 and Igkv6-14 in adriamycin combined quercetin group and quercetin group was lower than that in adriamycin group. The Ms4a1, Podx1, Mecom, Sh3bgr12, Bex4 and Tdrp expression in adriamycin combined quercetin group and adriamycin group were higher than that in quercetin group, while Crabp1 expression was lower.
CONCLUSION:Quercetin can inhibit the proliferation of primary leukemia cells in a time-dependent manner. Quercetin combined with adriamycin inhibit the proliferation of primary leukemia cells significantly, and had synergistic and additive effects on the proliferation of primary leukemia cells, and the inhibiting effect of quercetin combined with adriamycin is concentration-and time-dependent. Quercetin combined with high-dose adriamycin can significantly prolong the survival time of non-irradiated T-ALL leukemia mice and reduce the myocardial damage caused by adriamycin.
