Antitumor Effect of IL-12 Gene-modified Bone Marrow Mesenchymal Stem Cells Combined With Fuzheng Yiliu Decoction in an in Vivo Glioma Nude Mouse Model

Background: Glioma is a complex cancer with a high morbidity and high mortality. Bone marrow mesenchymal stem cells (BMSCs) have shown promise as an excellent cell/drug delivery vehicle for gene-targeted therapy; however, maintaining genetic stability and biological activity remains difficult. Furthermore, whether BMSCs support or inhibit tumor growth remains debated. This study investigated whether a traditional chinese medicine fomular, Fuzheng Yiliu decoction (FYD) had a synergistic antitumor effect with IL-12 gene-modified BMSCs in glioma-bearing nude mice. Methods: : The lentivirus-mediated IL-12 gene was transfected into primarily cultured BMSCs. A total of 72 BALB/c nude mice were used to establish xenograft models with glioma U251 cells and were divided into 6 groups (n = 12) including negative control group, nude mouse model group, lentiviral empty vector transfection into BMSC group, IL-12 gene lentivirus transfection into BMSC group and FYD treatment of IL-12 lentivirus-transfected BMSC group. After treatment for 14 days, all mice were sacrificed to collect tumor tissue and serum for more detection, such as distribution of BMSCs, cell apoptosis in xenograft tumors, serum IL-12 and INF-γ levels, mouse weight and tumor volume were measured. Results: : There were significantly more apoptotic cells in tumor tissue in IL-12 gene transfected group, FYD treatment group and FYD combining with IL-12 gene transfected group than that in the model group ( P < 0.05). The FYD+IL-12+BMSC group showed significantly higher Bax and lower Bcl-2 expression ( P < 0.05), and serum IL-12 and INF-γ levels ( P < 0.05) were higher than that in all other groups. After the intervention, this group also showed a strong inhibitory effect against tumor growth ( P < 0.05). Conclusions: : This study suggested FYD treatment combined with IL-12 gene-modified BMSCs shows synergistic antitumor effect in glioma-bearing nude mice.