Intervention Mechanism of Bushen Huoxuetang on Osteoporosis Related to Endocrine Therapy in Breast Cancer Based on PI3K/Akt/HIF-1α Signaling Pathway
10.13422/j.cnki.syfjx.20221014
- VernacularTitle:基于PI3K/Akt/HIF-1α信号通路探讨补肾活血汤干预乳腺癌内分泌治疗相关骨质疏松的作用机制
- Author:
Hongyi LIANG
1
;
Zhiyong LIU
2
;
Xiaofei LIU
3
;
Jingwei LI
2
Author Information
1. College of Traditional Chinese Medicine（TCM）， Shandong University of TCM， Jinan 250014， China
2. Affiliated Hospital of Shandong University of TCM， Jinan 250014， China
3. The First Clinical Medical College of Shandong University of TCM， Jinan 250014， China
- Publication Type:Journal Article
- Keywords:
Bushen Huoxuetang;
breast cancer;
osteoporosis;
phosphatidylinositol 3-kinases（PI3K）/protein kinase B（Akt）;
hypoxia-inducible factor-1α（HIF-1α）
- From:
Chinese Journal of Experimental Traditional Medical Formulae
2022;28(17):164-172
- CountryChina
- Language:Chinese
-
Abstract:
ObjectiveTo predict the underlying mechanism of Bushen Huoxuetang in treating osteoporosis related to endocrine therapy in breast cancer by network pharmacology and to verify the results through in vitro cell model. MethodThe main effective components and targets of Bushen Huoxuetang were screened out through network pharmacology， and the targets of osteoporosis related to endocrine therapy in breast cancer were further obtained. The intersected targets were analyzed by Gene Ontology （GO） functional annotation and Kyoto Encyclopedia of Genes and Genomes （KEGG） pathway enrichment. Kaplan Meier plotter was used to analyze the survival of crucial targets. Finally， the inhibitory activity against cell proliferation was evaluated by in vitro methye thiazolye telrazlium（MTT） assay. The key targets and pathways were verified by Western blot， and the mRNA expression of the key targets was evaluated by real-time polymerase chain reaction（Real-time PCR）. ResultA total of 716 active components and 249 key targets of Bushen Huoxuetang were obtained from network pharmacology. There were 135 common targets， among which protein kinase B（Akt）1 and hypoxia-inducible factor-1α （HIF-1α） were two key targets. Additionally， 531 biological processes， 62 cellular components， 162 molecular functions， and 145 signaling pathways including breast cancer and endocrine resistance were involved. The key targets were effectively enriched in phosphatidylinositol 3-kinases（PI3K）/Akt and HIF-1 signaling pathways. According to the MTT assay， the cell proliferation rate and cell motility of MCF-7 and T47D cells in the luminal A cell line were reduced by Bushen Huoxuetang treatment （22.5， 45， 90 g·L-1， and 45， 90， 180 g·L-1） for 48 h as compared with the blank group. As revealed by Western blot， MCF-7 cells were treated with Bushen Huoxuetang （0， 15， 60 g·L-1） for 48 h， and the relative expression of p-PI3K， PI3K， p-Akt， Akt， and HIF-1α was decreased in a dose-dependent manner as compared with the blank group （P<0.05， P<0.01）. Real-time PCR was used to detect the mRNA expression of the key target HIF-1α. The results showed that the mRNA expression of HIF-1α in MCF-7 cells was decreased with the increase in the dose （P<0.01）， and the change was in a concentration-dependent manner. ConclusionThe mechanism of Bushen Huoxuetang in the treatment of osteoporosis related to endocrine therapy in breast cancer may be related to the key targets including Akt1 and HIF-1α through the PI3K/Akt/HIF-1α signaling pathway.
