Mechanism of Pachymic Acid in Inhibiting Invasion and Metastasis of Renal Carcinoma Cells via Regulating MMP/TIMP Balance by Smads
10.13422/j.cnki.syfjx.202202127
- VernacularTitle:茯苓酸通过Smads调控MMP/TIMP平衡抑制肾癌细胞侵袭转移的机制
- Author:
Yuanyuan LUO
1
;
Xinyi FENG
1
;
Zewen CHU
1
;
Hong ZHU
1
;
Yanqing LIU
1
;
Haibo WANG
1
Author Information
1. Medical College，Key Laboratory of Syndrome Differentiation and Treatment of Gastric Cancer of State Administration of Traditional Chinese Medicine，Yangzhou University- Yangzhou Cancer Research Institute， Yangzhou University，Yangzhou 225001，China
- Publication Type:Journal Article
- Keywords:
pachymic acid;
renal carcinoma;
matrix metalloproteinase/tissue inhibitor of metalloproteinasas（MMP/TIMP）;
Smad2/3;
invasion and metastasis
- From:
Chinese Journal of Experimental Traditional Medical Formulae
2023;29(7):76-83
- CountryChina
- Language:Chinese
-
Abstract:
ObjectiveTo investigate the effect and mechanism of pachymic acid （PA） in Poria on the invasion and metastasis of renal carcinoma cells. MethodThe effect of PA （0， 20， 40， 80， 160 μmol·L-1） on cell viability was detected by cell counting kit-8（CCK-8）， and the dose of PA was selected for subsequent experiments. The effect of PA （0， 20， 40， 80 μmol·L-1） on cell proliferation was evaluated by colony formation assay. The effect of PA （0， 20， 40， 80 μmol·L-1） on cell adhesion ability was observed by cell adhesion assay. The effect of PA （0， 20， 40， and 80 μmol·L-1） on cell invasion and metastasis was investigated by Wound healing assay and Transwell invasion assay. The inhibitory effect of PA （0， 20， 40， 80 μmol·L-1） on cell motility was further observed and verified by high-content imaging technology. The effects of PA （0， 20， 40， 80 μmol·L-1） on the expression of matrix metalloproteinase （MMP）/tissue inhibitor of metalloproteinasas （TIMP） related to invasion and metastasis and Smads were detected by Western blot. ResultCCK-8 results showed that compared with the blank group， the PA groups showed decreased cell viability（P<0.01）， with the half-maximal inhibitory concentration （IC50） of ACHN cells of 70.42 μmol·L-1 at 24 h. Colony formation assay showed that the number of cell clonal groups in the PA groups was reduced compared with that in the blank group（P<0.01）. Cell adhesion assay showed that compared with the blank group， the PA groups displayed reduced cell adhesion（P<0.01）. Wound healing assay showed that the wound healing rate of cells in the PA groups was lower than that in the blank group （P<0.05，P<0.01）. Transwell invasion assay showed that compared with the blank group， the number of transmembrane cells in PA groups was reduced（P<0.01）. High-content imaging showed that the cumulative migration distance of cells in the PA groups was shorter than that in the blank group（P<0.01）. The results of Western blot showed that the protein expression of MMP-2 and MMP-9 in the PA groups decreased （P<0.01）， and TIMP-1 protein expression increased （P<0.01） compared with those in the blank group. In addition， compared with the blank group， the PA groups showed decreased protein expression of Smad2 and Smad3 （P<0.01）. ConclusionPA can inhibit the invasion and metastasis of renal carcinoma cells presumably through regulating the homeostasis of MMP/TIMP by Smad2/3.
