Upregulation of sulfatase-1 decreases metastatic potential of SKOV3 human ovarian cancer cells in vitro and in vivo.

Abstract

Sulfatase-1 (SULF-1) is one of the genes associated with the inhibition of several signaling pathways by desulfating HSPG in cancer cells. The aim of this study is to investigate the effect of SULF-1 upregulation on SKOV3 ovarian cancer cell line and its influence on cell proliferation, migration, invasion in vitro, and lymph node metastasis in 615 inbred mice in vivo. In in vitro study, we upregulated SULF-1 in SKOV3 cells using SULF-1 expression plasmid. Quantitative real-time reverse transcription-polymerase chain reaction (qRT-PCR) and western blotting were used to measure SULF-1 expression levels after stable upregulation. CCK-8, flow cytometry, Boyden Transwell-chamber, and scratch-wound healing assay were performed to explore the effect of SULF-1 on the proliferation, migration, and invasion. In in vivo study, immunohistochemistry and eosin stain (H and E) were used to evaluate the expression level of SULF-1 gene and to measure the lymph node metastatic rate of mice inoculated with SULF-1-SKOV3-expressed plasmid, SKOV3, and Nc-SKOV3 cells. qRT-PCR and western blot assay confirmed that SULF-1 was upregulated both in mRNA and protein levels. Following SULF-1 stable upregulation, the cell proliferation, migration, and invasion were significantly reduced in the SULF-1 upregulated cells (SULF-1-SKOV3) compared with the nontransfected (SKOV3) and the nonspecific sequence transfected cells (Nc-SKOV3). IHC results showed that SULF-1 was highly expressed after stably upregulation in SKOV3 cells, and H and E stain confirmed that the mice inoculated with SULF-1-SKOV3 cells decreased lymph node metastatic rate compared to the two control groups. Our findings showed that overexpression of SULF-1 in SKOV3 results in a decrease in ovarian cancer cell proliferation, migration, and invasion in vitro and decreased lymph node metastasis in vivo. This finding could have a potential therapeutic window in the management of ovarian cancer.