Acteoside promotes autophagy and apoptosis of hepatoma cells by regulating JNK signaling pathway.
10.19540/j.cnki.cjcmm.20221222.402
- Author:
Yu-Jing HE
1
;
Ying ZHENG
1
;
Chu-Yi LI
1
;
Liu-Lu GAO
1
;
Jun-Ke WANG
1
;
Bin LI
1
;
Li-Xia LU
1
;
Pan WANG
1
;
Xiao-Hui YU
1
;
Jiu-Cong ZHANG
1
Author Information
1. Department of Gastroenterology, the 940th Hospital of Joint Logistics Support Force of Chinese People's Liberation Army Lanzhou 730050, China.
- Publication Type:Journal Article
- Keywords:
H22 tumor-bearing mice;
JNK signaling pathway;
acteoside;
apoptosis;
autophagy
- MeSH:
Male;
Animals;
Mice;
Cisplatin/pharmacology*;
Carcinoma, Hepatocellular/genetics*;
MAP Kinase Signaling System;
Beclin-1;
Apoptosis;
Liver Neoplasms/genetics*;
Necrosis;
Proto-Oncogene Proteins c-bcl-2/metabolism*;
Cell Line, Tumor;
RNA, Messenger/metabolism*;
Autophagy
- From:
China Journal of Chinese Materia Medica
2023;48(9):2343-2351
- CountryChina
- Language:Chinese
-
Abstract:
This study explored the molecular mechanism of acteoside against hepatoma 22(H22) tumor in mice through c-Jun N-terminal kinase(JNK) signaling pathway. H22 cells were subcutaneously inoculated in 50 male BALB/c mice, and then the model mice were classified into model group, low-dose, medium-dose, and high-dose acteoside groups, and cisplatin group. The administration lasted 2 weeks for each group(5 consecutive days/week). The general conditions of mice in each group, such as mental status, diet intake, water intake, activity, and fur were observed. The body weight, tumor volume, tumor weight, and tumor-inhibiting rate were compared before and after administration. Morphological changes of liver cancer tissues were observed based on hematoxylin and eosin(HE) staining, and the expression of phosphorylated(p)-JNK, JNK, B-cell lymphoma-2(Bcl-2), Beclin-1, and light chain 3(LC3) in each tissue was detected by immunohistochemistry and Western blot. qRT-PCR was performed to detect the mRNA expression of JNK, Bcl-2, Beclin-1, and LC3. The general conditions of mice in model and low-dose acteoside groups were poor, while the general conditions of mice in the remaining three groups were improved. The body weight of mice in medium-dose acteoside group, high-dose acteoside group, and cisplatin group was smaller than that in model group(P<0.01). The tumor volume in model group was insignificantly different from that in low-dose acteoside group, and the volume in cisplatin group showed no significant difference from that in high-dose acteoside group. Tumor volume and weight in medium-dose and high-dose acteoside groups and cisplatin group were lower than those in the model group(P<0.001). The tumor-inhibiting rates were 10.72%, 40.32%, 53.79%, and 56.44% in the low-dose, medium-dose, and high-dose acteoside groups and cisplatin group, respectively. HE staining showed gradual decrease in the count of hepatoma cells and increasing sign of cell necrosis in the acteoside and cisplatin groups, and the necrosis was particularly obvious in the high-dose acteoside group and cisplatin group. Immunohistochemical results suggested that the expression of Beclin-1, LC3, p-JNK, and JNK was up-regulated in acteoside and cisplatin groups(P<0.05). The results of immunohistochemistry, Western blot, and qRT-PCR indicated that the expression of Bcl-2 was down-regulated in the medium-dose and high-dose acteoside groups and cisplatin group(P<0.01). Western blot showed that the expression of Beclin-1, LC3, and p-JNK was up-regulated in acteoside and cisplatin groups(P<0.01), and there was no difference in the expression of JNK among groups. qRT-PCR results showed that the levels of Beclin-1 and LC3 mRNA were up-regulated in the acteoside and cisplatin groups(P<0.05), and the level of JNK mRNA was up-regulated in medium-dose and high-dose acteoside groups and cisplatin group(P<0.001). Acteoside promotes apoptosis and autophagy of H22 cells in mice hepatoma cells by up-regulating the JNK signaling pathway, thus inhibiting tumor growth.
