Yanghe Huayantang Reverses Tamoxifen Resistance in Breast Cancer Through ER/PI3K/Akt/mTOR Pathway
10.13422/j.cnki.syfjx.20210621
- VernacularTitle:阳和化岩汤通过ER/PI3K/Akt/mTOR通路逆转乳腺癌他莫昔芬耐药
- Author:
Qian-qian XU
1
;
Lei WANG
2
;
Zhi-yong LIU
2
;
Xue SUN
1
;
Run-jia LUO
3
;
Xing-yu WANG
3
;
Xiao-fei LIU
3
;
Jing-wei LI
2
Author Information
1. College of Traditional Chinese Medicine（TCM）， Shandong University of TCM， Ji´nan 250014，China
2. Affiliated Hospital of Shandong University of TCM， Ji´nan 250014，China
3. The First Clinical Medical College of Shandong University of TCM， Ji´nan 250014，China
- Publication Type:Research Article
- Keywords:
Yanghe Huayantang;
estrogen receptor（ER）/phosphatidylinositol 3-kinase（PI3K）/protein kinase B（Akt）/rapamycin target（mTOR） protein signaling pathway;
breast cancer;
tamoxifen;
everolimus
- From:
Chinese Journal of Experimental Traditional Medical Formulae
2021;27(7):34-41
- CountryChina
- Language:Chinese
-
Abstract:
Objective:To explore the possible mechanism of Yanghe Huayantang in reversing the drug resistance of breast cancer by observing the effect of Yanghe Huayantang on the transplant tumor of tamoxifen （TAM）-resistant breast cancer and its influences on the interaction pathway of estrogen receptor （ER）/phosphatidylinositol 3-kinase （PI3K）/protein kinase B （Akt）/mammalian rapamycin target protein （mTOR）. Method:Fifty mice were randomly divided into 5 groups： blank group， model group， Yanghe Huayantang group， everolimus group， and Yanghe Huayantang+everolimus group. The model of kidney deficiency was established by bilateral ovariectomy， and the blank group was treated with sham operation. Three days after the establishment of the model， all the five groups of mice were inoculated with breast cancer TAM drug-resistant cells （MCF-7/TAM-） to establish breast cancer TAM -resistant transplanted tumor model. After successful modeling， Yanghe Huayantang group received intragastric administration of Yanghe Huayantang （traditional Chinese medicine preparation 20 mL·kg-1）， everolimus group received intraperitoneal injection of everolimus （10 mg·kg-1）. Yanghe Huayantang + everolimus group received Yanghe Huayantang by intragastric administration and everolimus by intraperitoneal injection. The blank group and model group received intragastric administration and intraperitoneal injection of phosphate buffer （PBS）. Drug administration was lasted for 28 days in all groups， once a day. After administration， the tumor tissue was separated and weighed， and the tumor inhibition rate was calculated. Hematoxylin-eosin （HE） staining was used to observe the pathological changes of tumor tissue. Immunofluorescence and Real-time fluorescence quantitative polymerase chain reaction （Real-time PCR） were used to detect the expression of PI3K， Akt， mTOR， ER protein and mRNA in tumor tissue. Result:Compared with the model group， the tumor volume and tumor weight of Yanghe Huayantang group decreased significantly on the 12th， 20th and 28th days （P<0.01）， and the tumor inhibition rate increased significantly （P<0.01）.Yanghe Huayantang group significantly reduced the density of tumor cells and caused tumor cell necrosis. Compared with the model group， Yanghe Huayantang group， everolimus group and Yanghe Huayantang+everolimus group inhibited the expression of PI3K， Akt， mTOR protein and mRNA （P<0.05， P<0.01）. Compared with the blank group， Yanghe Huayantang group， everolimus group and Yanghe Huayantang+everolimus group all inhibited the protein and mRNA expression of ER， and mRNA expression of ER in Yanghe Huayantang+everolimus group was significantly lower than that in the model group （P<0.01）. Conclusion:Yanghe Huayantang can inhibit the growth of TAM-resistant breast cancer. The mechanism may be that Yanghe Huayantang can reverse the TAM resistance of breast cancer by down-regulating the expression of key molecules of ER/PI3K/Akt/mTOR cross-signal pathway.
