Effects of increasing efficacy and decreasing toxicity of ginkgo flavone aglycone on doxorubicin in the treatment of liver cancer
- VernacularTitle:银杏黄酮苷元对多柔比星治疗肝癌的增效减毒作用
- Author:
Zhongjun SONG
1
;
Xiaoqing ZHU
1
;
Yan HE
2
;
Yongjun LI
3
;
Yuan LU
4
Author Information
1. Guizhou Provincial Key Laboratory of Pharmaceutics/State Key Laboratory of Functions and Applications of Medicinal Plants，Guizhou Medical University，Guiyang 550004，China;School of Pharmacy，Guizhou Medical University，Guiyang 550004，China
2. Clinical Trial Research Center，the Affiliated Hospital of Guizhou Medical University，Guiyang 550004，China
3. School of Pharmacy，Guizhou Medical University，Guiyang 550004，China;Engineering Research Center for the Development and Application of Ethnic Medicine and TCM（Ministry of Education ），Guizhou Medical Univer sity，Guiyang 550004，China
4. Guizhou Provincial Key Laboratory of Pharmaceutics/State Key Laboratory of Functions and Applications of Medicinal Plants，Guizhou Medical University，Guiyang 550004，China
- Publication Type:Journal Article
- Keywords:
ginkgo flavone aglycone;
doxorubicin;
efficacy enhancing and toxicity reducing;
liver cancer;
H22 tumor-bearing mice
- From:
China Pharmacy
2022;33(16):1937-1942
- CountryChina
- Language:Chinese
-
Abstract:
OBJECTIVE To study the effects of increasing efficacy and decreasing toxicity of ginkgo flavone aglycone （GA） on doxorubicin （DOX）in the treatment of liver cancer. METHODS A tumor bearing model was established by inoculating liver cancer cell H 22 into the right axillary skin of ICR mice. The successfully modeled mice were randomly divided into model control group，DOX group （2.5 mg/kg，once every other day ，via tail vein ），GA group （30 mg/kg，once a day ，gavage）and GA+DOX group（the usage was the same as single drug groups ），with 6 mice in each group. The administration cycle was 15 days. The general growth of mice in each group were observed ，body weight and tumor weight were measured ，and the inhibition rate of tumor was calculated. Jin’s formula was used to evaluate the effect of combined medication （Q）. The serum level of alpha-fetal protein（AFP），the pathological changes of tumor tissue ，cell apoptosis and the expression of platelet-endothelial cell adhesion molecule-1（CD31）were detected in each group. The cardiac index，serum levels of B-type natriuretic peptide （BNP）and N-terminal pro-brain natriuretic peptide （NT-pro BNP ），pathological changes of heart and myocardial fibrosis degree were also detected. RESULTS The percentage of body weight change （except for GA group ） and tumor weights of DOX group，GA group and GA + DOX group were all decreased significantly，compared with model control group （P＜0.05 or P＜0.01），while tumor weight of GA+DOX gro up was significantly lower than DOX group （P＜0.01）. Inhibitory rates of tumor in 3 administration groups were 54.29％，42.50％ and 89.29％ respectively，and Q of two-drug combination was 1.21. The tumor tissues of mice in each administration group were necrotic to varying degrees ；the serum level of AFP and the expression of CD31 in tumor tissue were decreased significantly ，compared with model control group （P＜0.05 or P＜0.01）；the percentage of necrosis area of tumor tissue and the positive rate of apoptosis （except for single drug groups ）were significantly increased （P＜0.05 or P＜0.01），while positive rate of apoptosis in GA+DOX group was significantly higher than DOX group （P＜0.05）. Cardiac index of mice in DOX group was significantly lower than model control group （P＜0.01）；serum levels of BNP and NT-pro BNP in DOX group and GA+ DOX group were significantly higher than model control group （P＜0.05 or P＜0.01）；pathological changes of heart and the degree of myocardial fibrosis in GA+DOX group were lower than DOX group. CONCLUSIONS GA combined with DOX show synergistic antitumor effect. GA can strengthen the apoptosis promoting effect of DOX ，and can help to reduce the cardiotoxicity of DOX.
