[Human umbilical cord mesenchymal stem cells with adenovirus-mediated interleukin 12 gene transduction inhibits the growth of ovarian carcinoma cells both in vitro and in vivo]

Abstract

Objective: To study the inhibitory effect of human umbilical cord mesenchymal stem cells (UC-MSCs) infected by a adenoviral vector containing interleukin 12 (IL-12) gene on the proliferation of ovarian carcinoma SKOV3 in vitro and the growth of tumor explants in nude mice.

Methods: Cultured human UC-MSCs were infected with the recombinant adenovirus vector harboring IL-12 gene to establish the IL-12-expressing cell line AdIL-12-MSCs. Western blotting and RT-PCR were used to detect IL-12 expressions in AdIL-12-MSCs at the protein and mRNA levels, respectively. ELISA were used to detect IL-12 content in the supernatant of AdIL-12-MSCs, whose effect on the proliferation and apoptosis of ovarian carcinoma SKOV3 cells was evaluated with MTT assay and flow cytometry, respectively. In a nude mouse model bearing subcutaneous SKOV3 tumor explants, AdIL-12-MSCs were infused via the tail vein and the inhibitory effect on the tumor growth was observed.

Results: The exogenous IL-12 gene was successfully transduced into UC-MSCs by the recombinant adenovirus vector, resulting in efficient IL-12 expression in the cell at both the protein and mRNA levels. The supernatant of AdIL-12-MSCs significantly inhibited the proliferation of SKOV3 cells and induced cellular apoptosis in vitro as compared with UC-MSC supernatant. In the tumor-bearing nude mouse model, the transplantation of AdIL-12-MSCs significantly inhibited the growth of SKOV3 tumor explants (P<0.05).

Conclusion: Human UC-MSCs with IL-12 gene transduction, which express IL-12 at protein and mRNA levels, can inhibit the proliferation and induce apoptosis of ovarian carcinoma SKOV3 cells in vitro, and suppress the growth of ovarian cancer explants in nude mice.