[논문]Steroidal Saponins from Paris polyphylla Suppress Adhesion, Migration and Invasion of Human Lung Cancer A549 Cells Via Down-Regulating MMP-2 and MMP-9

He, Hao; Zheng, Lei; Sun, Yan-Ping; Zhang, Guang-Wei; Yue, Zheng-Gang

doi:10.7314/apjcp.2014.15.24.10911

Steroidal Saponins from Paris polyphylla Suppress Adhesion, Migration and Invasion of Human Lung Cancer A549 Cells Via Down-Regulating MMP-2 and MMP-9 원문보기

Asian Pacific journal of cancer prevention : APJCP, v.15 no.24, 2014년, pp.10911 - 10916

He, Hao (School of Pharmaceutical Sciences, Xi'an Medical University) , Zheng, Lei (School of Pharmaceutical Sciences, Xi'an Medical University) , Sun, Yan-Ping (School of Pharmaceutical Sciences, Xi'an Medical University) , Zhang, Guang-Wei (Clinical Medicine College, Xi'an Medical University) , Yue, Zheng-Gang (Shanxi Collaborative Innovation Center of Chinese Medicinal Resource Industrialization, School of Pharmacy, Shanxi College of Traditional Chinese Medicine)

Abstract ▼ AI-Helper

Background: Tumor metastases are the main reasons for oncotherapy failure. Paris polyphylla (Chinese name: Chonglou) has traditionally been used for its anti-cancer actions. In this article, we focus on the regulation of human lung cancer A549 cell metastases and invasion by Paris polyphylla steroidal saponins (PPSS). Materials and Methods: Cell viability was evaluated in A549 cells by MTT assay. Effects of PPSS on invasion and migration were investigated by wound-healing and matrigel invasion chamber assays. Adhesion to type IV collagen and laminin was evaluated by MTT assay. Expression and protease activity of two matrix metalloproteinases (MMPs), MMP-2 and MMP-9, were analyzed by Western blotting and gelatin zymography, respectively. Results: PPSS exerted growth inhibitory effects on A549 cells, and effectively inhibited A549 cell adhesion, migration and invasion in a concentration-dependent manner. Western blotting and gelatin zymography analysis revealed that PPSS inhibited the expression and secretion of MMP-2 and MMP-9 in A549 cells. Conclusions: PPSS has the potential to suppress the migration, adhesion and invasion of A549 cells. PPSS could be a potential candidate for interventions against lung cancer metastases.

주제어

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All the presented data and results were confirmed in at least three independent experiments and were expressed as mean±S.D. Statistical comparisons were made by Student’s t-test and One-way ANOVA followed by Tukey’s post hoc test.

이론/모형

A549 cells were treated with various concentrations of PPSS for 12, 24 and 48 h. Cell viability was measured by MTT assay. Data were represented as means±S.

성능/효과

, 2014). After diagnosis of the disease, the average 5 year survival rate is reported to be 5-10%. Metastasis is the final stage in tumor progression from a normal cell to a fully malignant cell, and is the cause of 90% of all deaths from cancer (Yilmaz et al.
After 24 h of treatment with 0, 20, 40, 80 mg/L PPSS, the cell number on the lower surface of the membrane decreased in a concentration-dependent manner (Figure 2B-C). All the results showed that PPSS could impair A549 cell migration.
In conclusion, these results indicated that PPSS was able to inhibit lung cancer cell adhesion, migration and invasion, the mechanism underlying was attributed to attenuation of the activity and expression of MMP-2 and MMP-9. With the undermining of the interrelation, PPSS would be a potential candidate for interventions against lung cancer metastases.
A) The cells were lysed after treatment with various concentrations of PPSS for 24 h and the protein levels of MMP-2 and MMP-9 were determined by western blot analysis. It showed that PPSS could inhibit the MMP-2 and MMP-9 expression in a concentration-dependent manner. GAPDH was used as a loading reference.
B) Gelatin zymogragpy analysis of serum-free media conditioned by A549 cells treated with 0, 20, 40 and 80 mg/L of PPSS. Results indicated that PPSS could exert an inhibitive effect on the secretion of MMP-2 and MMP-9 in a concentration-dependent manner compared with the control group. C) Quantification of the gelatin zymography assay.
These results reveal that PPSS’s anti-invasive action is associated with diminishing the ability of lung cancer cells to degrade the components of ECM by modulating MMP-2 and MMP-9 expression and activity.

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