title: Matrine suppresses invasion of castration-resistant prostate cancer cells by downregulating MMP-2/9 via NF-κB signaling pathway.
abstract: Matrine is an alkaloid from Sophora flavescens that exhibits multiple protective effects on cancers. However, the molecular mechanisms of anti-metastatic effects of matrine on castration-resistant prostate cancer (CRPC) remain unknown. This study investigated the anti-metastatic effects of matrine on CRPC to identify the underlying mechanisms. The effects of matrine on the cell viability of DU145 and PC-3 cells were measured using MTS assay. The impact of matrine on expression levels of matrix metalloproteinase (MMP)-9, MMP-2, nuclear factor-κB (NF-κB) subunit p65 and phosphorylated p65 in cells untreated or treated with matrine were analyzed by western blotting. The inhibitory effects of matrine on cell migration and invasion were examined by Transwell assay. The impact of matrine on tumorigenesis in male Balb/c nude mice inoculated subcutaneously with cells were investigated in vivo. We found that matrine inhibited the growth of DU145 and PC3 cells time- and dose-dependently both in vitro and in vivo. Migration and invasion capabilities of cells were also suppressed by matrine. At the same time, matrine markedly reduced the expression levels of MMP-9, MMP-2 and p-p65 in both cell lines. Further experiments revealed that matrine exhibited inhibitory effects of migration and invasion of CRPC by downregulating MMP-2/9 through NF-κB pathway. Matrine inhibits invasion of CRPC by reducing levels of MMP-9 and MMP-2 through NF-κB pathway. Therefore, it may be a potential anti-metastatic therapeutic agent for CRPC.
authors.affiliation: Department of Urology, Sun Yat-sen Memorial Hospital, Sun Yat-sen University, Haizhu, Guangzhou, Guangdong 510220, P.R. China.
authors.forename: Hai
authors.initials: H
authors.lastname: Huang
authors.affiliation: Guangdong Provincial Key Laboratory of Malignant Tumor Epigenetics and Gene Regulation, Sun Yat-sen Memorial Hospital, Sun Yat-sen University, Guangzhou, Guangdong 510120, P.R. China.
authors.forename: Tao
authors.initials: T
authors.lastname: Du
authors.affiliation: Center for Translational Cancer Research, Institute of Biosciences and Technology, Texas A&M Health Science Center, Houston, TX 77030, USA.
authors.forename: Guibin
authors.initials: G
authors.lastname: Xu
authors.affiliation: Department of Urology, Sun Yat-sen Memorial Hospital, Sun Yat-sen University, Haizhu, Guangzhou, Guangdong 510220, P.R. China.
authors.forename: Yiming
authors.initials: Y
authors.lastname: Lai
authors.affiliation: Department of Urology, Sun Yat-sen Memorial Hospital, Sun Yat-sen University, Haizhu, Guangzhou, Guangdong 510220, P.R. China.
authors.forename: Xinxing
authors.initials: X
authors.lastname: Fan
authors.affiliation: Department of Urology, Sun Yat-sen Memorial Hospital, Sun Yat-sen University, Haizhu, Guangzhou, Guangdong 510220, P.R. China.
authors.forename: Xianju
authors.initials: X
authors.lastname: Chen
authors.affiliation: Center for Translational Cancer Research, Institute of Biosciences and Technology, Texas A&M Health Science Center, Houston, TX 77030, USA.
authors.forename: Wenjiao
authors.initials: W
authors.lastname: Li
authors.affiliation: Center for Translational Cancer Research, Institute of Biosciences and Technology, Texas A&M Health Science Center, Houston, TX 77030, USA.
authors.forename: Fei
authors.initials: F
authors.lastname: Yue
authors.affiliation: Department of Clinical Laboratory, Xiyuan Hospital, China Academy of Chinese Medical Sciences, Haidian, Beijing 100091, P.R. China.
authors.forename: Qi
authors.initials: Q
authors.lastname: Li
authors.affiliation: Center for Translational Cancer Research, Institute of Biosciences and Technology, Texas A&M Health Science Center, Houston, TX 77030, USA.
authors.forename: Leyuan
authors.initials: L
authors.lastname: Liu
authors.affiliation: Department of Urology, Sun Yat-sen Memorial Hospital, Sun Yat-sen University, Haizhu, Guangzhou, Guangdong 510220, P.R. China.
authors.forename: Kaiwen
authors.initials: K
authors.lastname: Li
mesh_terms: D000470:Alkaloids / Q000008:administration & dosage* / Q000494:pharmacology; D000818:Animals; D000972:Antineoplastic Agents, Phytogenic / Q000008:administration & dosage* / Q000494:pharmacology; D045744:Cell Line, Tumor; D002465:Cell Movement / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects; D006801:Humans; D008297:Male; D020778:Matrix Metalloproteinase 2 / Q000378:metabolism*; D020780:Matrix Metalloproteinase 9 / Q000378:metabolism*; D051379:Mice; D016328:NF-kappa B / Q000378:metabolism*; D009361:Neoplasm Invasiveness; D064129:Prostatic Neoplasms, Castration-Resistant / Q000188:drug therapy* / Q000378:metabolism; D011807:Quinolizines / Q000008:administration & dosage* / Q000494:pharmacology; D015398:Signal Transduction / Q000187:drug effects; D023041:Xenograft Model Antitumor Assays; D000093842:Matrines
chemical_list: D000470:Alkaloids; D000972:Antineoplastic Agents, Phytogenic; D016328:NF-kappa B; D011807:Quinolizines; C522361:MMP2 protein, human; D020778:Matrix Metalloproteinase 2; C579270:MMP9 protein, human; D020780:Matrix Metalloproteinase 9; D000093842:Matrines