The effect of endostatin mediated by human mesenchymal stem cells on ovarian cancer cells in vitro

Abstract

Endostatin is the most potent inhibitor of tumor angiogenesis. However, endostatin protein has a short half-time and virus-mediated endostatin gene therapy has serious toxicity, which limits the application of endostatin in clinical therapy. Mesenchymal stem cells (MSCs) are considered to be able to accumulate at the site of cancers with high specificity and may be used as a new delivery of endostatin. The MSCs from the human bone marrow were transfected with recombinant adenovirus encoding endostatin and EGFP (MSC-EN cells). The tropism capacity of MSCs was quantitatively assayed in vitro using the Millicell system. To investigate the impact of secreted endostatin on cancer cells, SKOV3 cells were co-cultured with MSC-EN cells in Millicell for 48 h, then apoptosis and cell cycle were analyzed on a flow cytometer. In contrast with 293 cells and saline, SKOV3 cells significantly stimulated migration of MSCs, the number reached 919.67 +/- 19.96 (P < 0.05). The endostatin produced by MSC-EN cells made 13.08 +/- 0.21% SKOV3 cells undergo early stage apoptosis (control 3.23 +/- 0.73%, P < 0.05) and 82.05 +/- 2.65% SKOV3 cells accumulate in the G0/G1 phase (control 66.51 +/- 2.91%, P < 0.05). We found that MSCs possessed great migratory capacity in vitro and the human ovarian adenocarcinoma cell line SKOV3 could significantly induce the migration of MSCs. Our results provided evidence that MSCs could be utilized as a powerful delivery system of endostatin. The endostatin produced by MSC-EN cells could inhibit the proliferation of SKOV3 cells.