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.

Matrine inhibits the progression of prostate cancer by promoting expression of GADD45B

“…KEGG pathway analysis of 1240 common differential genes revealed the top 10 enriched pathways related to integrin, apoptosis, angiogenesis, platelet‐derived growth factor (PDGF), P53, Wnt, vascular endothelial growth factor (VEGF), PI3 kinase, p38/MAPK, and cell cycle (Figure B). Our previous results show a close relationship between matrine and cell apoptosis so that genes related apoptosis were selected to be further analyzes (Figure C).…”

“…Other studies have shown that matrine can block cell cycle in G1 phase, S phase, or G2/M period . The observed synergistic impacts may be caused by either promoting the expression of GADD45B gene or through other signaling pathways such as EGFR/ERK/MMP‐2, AKT/GSK3β/β‐catenin, and PTEN/AKT to inhibit tumor cell progression . It is unknown whether matrine will promote or inhibit autophagy.…”

“…Numerous studies have shown that matrine can inhibit tumor progression not only by inhibiting EGFR/ERK/MMP‐2, AKT/GSK3β/β‐catenin, and PTEN/AKT pathways, but also by enhancing the expression of chemokine receptor 7 (CCR7) to down‐regulate the expression of proinflammatory cytokines IL‐1β and IL‐17 to improve the status of intestinal inflammation . Most importantly, matrine can downregulate the expression of MMP2 and MM9 by modulating the NF‐κB pathway to reduce the proliferation, migration and invasion of prostate cancer cells . However, the molecular mechanism for matrine to inhibit the progression of prostate cancer has not been fully elucidated yet.…”

Recent Progress on the Molecular Mechanisms of Anti-invasive and Metastatic Chinese Medicines for Cancer Therapy

“…Such inhibition on colorectal cancer cells was also observed when treated with 2,3,5,4′-tetrahydroxystilbene-2-O-β-D-glucoside [49]. As an alkaloid derived from Sophora flavescens, matrine can inhibit the invasion and migration of castration-resistant prostate cancer DU145 and PC3 cells by suppressing MMP-9 and MMP-2 expressions through NF-κB pathway [50]. The phenol derived from Taiwanese edible fungus Antrodia cinnamomea, 2,3,5-trimethoxy-4-cresol, was recently described as an effective antimetastatic agent against lung cancer via suppressing Akt, MMP-2 and MMP-9, and increasing E-cadherin and TIMP-1 [51].…”

<p>Matrine Restrains Cell Growth and Metastasis by Up-Regulating LINC00472 in Bladder Carcinoma</p>

“…Researches have pointed out MAT can conspicuously restrain prostate carcinoma. 13 In addition, a research has pointed out that MAT restrains the activity of BC cells. 14 Many types of researches have pointed out that the development of malignant carcinomas usually results from abnormal gene expression.…”