Liquiritigenin Potentiates the Inhibitory Effects of Cisplatin on Invasion and Metastasis Via Downregulation MMP-2/9 and PI3 K/AKT Signaling Pathway in B16F10 Melanoma Cells and Mice Model

Abstract

Liquiritigenin (LQ) is a flavanone extracted from glycyrrhizae. Previous studies have demonstrated that LQ possesses antimigration properties in HELA and A549 cells. The present research, as an extension of our earlier ones, investigated whether LQ can enhance the antimigration and antiinvasion effect of cis-diamine dichloroplatinum (CDDP) in B16F10 melanoma cell. The data indicated that LQ (25, 50, 100, 200 μM) combined with CDDP (2 μM) significantly reduced B16F10 cell viability compared to CDDP (2 μM)-treated only. The different doses of LQ combined with CDDP significantly suppressed cell migration (21.5%, 49.6%, 75.6%) and cell invasion (26.2%, 51.4%, 69.5%) compared with CDDP-treated alone, suggesting that LQ enhance the inhibition action of CDDP on cell migration and invasion. Moreover, LQ/CDDP combination led to the downregulation of protein expression of MMP-2/9, PI3 K, p-AKT, and upregulated PTEN protein level that play an important role in tumor metastasis progression. Further study demonstrated the enhancement effect of LQ on CDDP suppressing lung metastasis in a mice model being inoculated by the B16F10 melanoma cells. In conclusion, the results suggested that LQ plays an intensive role on CDDP suppressing invasion and metastasis through regulating the PI3 K/AKT signal pathway and suppressing the protein expression of MMP-2/9.

ACKNOWLEDGMENTS

We thank Yu-Chen Wu, Fei Jiang, Xue-Min Wang and Zhi-Min Chen (Nanjing Medical University, China) for their technical assistance.

FUNDING

This work was supported by the National Natural Science Foundation of China (No. 30972478) and the Priority Academic Program Development of Jiangsu Higher Education institutions (China).