title: 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.
authors.affiliation: a Department of Nutrition and Food Hygiene , School of Public Health, Nanjing Medical University , Nanjing , China.
authors.forename: Hui
authors.initials: H
authors.lastname: Shi
authors.forename: Yuchen
authors.initials: Y
authors.lastname: Wu
authors.forename: Yang
authors.initials: Y
authors.lastname: Wang
authors.forename: Ming
authors.initials: M
authors.lastname: Zhou
authors.forename: Shu
authors.initials: S
authors.lastname: Yan
authors.forename: Zhimin
authors.initials: Z
authors.lastname: Chen
authors.forename: Dawei
authors.initials: D
authors.lastname: Gu
authors.forename: Yunqing
authors.initials: Y
authors.lastname: Cai
mesh_terms: D000818:Animals; D000970:Antineoplastic Agents / Q000627:therapeutic use; D045744:Cell Line, Tumor; D002465:Cell Movement / Q000187:drug effects; D002945:Cisplatin / Q000627:therapeutic use*; D015536:Down-Regulation / Q000187:drug effects; D004357:Drug Synergism; D005260:Female; D044950:Flavanones / Q000494:pharmacology*; D008175:Lung Neoplasms / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D020778:Matrix Metalloproteinase 2 / Q000378:metabolism*; D020780:Matrix Metalloproteinase 9 / Q000378:metabolism*; D008546:Melanoma, Experimental / Q000188:drug therapy* / Q000378:metabolism / Q000556:secondary; D051379:Mice; D008810:Mice, Inbred C57BL; D023421:Models, Animal; D009361:Neoplasm Invasiveness / Q000517:prevention & control; D019869:Phosphatidylinositol 3-Kinases / Q000378:metabolism*; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism*; D015398:Signal Transduction / Q000187:drug effects
chemical_list: D000970:Antineoplastic Agents; D044950:Flavanones; D019869:Phosphatidylinositol 3-Kinases; D051057:Proto-Oncogene Proteins c-akt; D020778:Matrix Metalloproteinase 2; C522362:Mmp2 protein, mouse; D020780:Matrix Metalloproteinase 9; C501830:Mmp9 protein, mouse; D002945:Cisplatin; C083152:liquiritigenin