Astragalus Polysaccharides Improve Cisplatin Resistance by Inhibiting EMT of Lung Adenocarcinoma A549/DDP Cells Transplanted into Nude Mice
10.13422/j.cnki.syfjx.20220527
- VernacularTitle:黄芪多糖抑制肺腺癌A549/DDP细胞移植瘤裸鼠EMT改善顺铂耐药的机制
- Author:
Ying ZHANG
1
;
Chun WANG
2
;
Dan YU
2
;
Yuan GAO
2
;
Huan JING
2
;
Ying WANG
2
;
Chun-ying LIU
2
Author Information
1. Jining Medical University，Jining 272000，China
2. Liaoning University of Traditional Chinese Medicine，Shenyang 110032，China
- Publication Type:Journal Article
- Keywords:
Astragalus polysaccharide;
epithelial mesenchymal transformation （EMT）;
cisplatin resistance;
lung adenocarcinoma
- From:
Chinese Journal of Experimental Traditional Medical Formulae
2022;28(6):79-85
- CountryChina
- Language:Chinese
-
Abstract:
ObjectiveTo investigate the inhibitory effect of Astragalus polysaccharide （APS） on epithelial-mesenchymal transition （EMT） induced by transforming growth factor-β1 （TGF-β1） in cisplatin （DDP）-resistant lung adenocarcinoma cell line A549/DDP cells transplanted into nude mice and the molecular mechanism in improving DDP resistance. MethodBALB/c nude mice were randomly divided into a blank group， a model group， a DDP group， and a combination group （APS combined with DDP）. A549/DDP cells were infected with TGF-β1-overexpressed lentiviral vector and the negative control. The infected cells were inoculated subcutaneously in nude mice. The A549/DDP cells with TGF-β1 gene overexpression were inoculated into all groups except the control group with negative TGF-β1 gene overexpression. The drug intervention was performed eight days after cell inoculation. The mice in the combination group received intragastric administration of APS （0.3 g·kg-1·d-1） and intraperitoneal injection of cisplatin （0.003 5 g·kg-1）， and those in the cisplatin group received intraperitoneal injection of cisplatin （0.003 5 g·kg-1）. After 32 days of cell inoculation， the nude mice were killed and the tumor tissues and lungs were collected. The tumor weight was recorded and the inhibition rate was calculated. The number of metastatic nodules of the lung tumor on the whole slide was counted under the microscope. Immunohistochemistry， Western blot， and real-time fluorescence-based quantitative polymerase chain reaction （Real-time PCR） were used to detect the protein and gene expression of EMT molecular markers α-catenin and N-cadherin， and tumor drug resistance markers human lung resistance protein （LRP）， multidrug resistance-associated protein （MRP）， and P-glycoprotein （P-gp） in the transplanted tumor. ResultCompared with the blank group， the model group showed increased tumor weight and metastatic nodules of the lung tumor （P<0.05）， decreased protein and mRNA expression of α-catenin （P<0.05）， and elevated protein and mRNA expression of N-cadherin， LRP， MRP， and P-gp （P<0.05）. Compared with the model group and the cisplatin group， the combination group showed reduced tumor weight and metastatic nodules of the lung tumor （P<0.05）， increased protein and mRNA expression of α-catenin （P<0.05）， and decreased protein and mRNA expression of N-cadherin， LRP， MRP， and P-gp （P<0.05）. ConclusionAPS can inhibit the growth and metastasis of the transplanted tumor of lung adenocarcinoma and improve cisplatin resistance， which may be related to the inhibition of EMT of tumor cells.
