Effect of IL-12 recombinant plasmid combined with bone marrow mesenchymal stem cells on the invasion of MCF-7 human breast cancer cells and the growth of nude mice xenografts

Abstract

Objective To investigate the effect of IL-12 recombinant plasmid combined with bone marrow mesenchymal stem cells (BMSC) on the invasion of MCF-7 breast cancer cells and the growth of transplanted tumor in nude mice. Methods BMSC cells were isolated, purified and cultured, and BMSC conditioned medium was prepared. The effects of BMSC conditioned medium on proliferation and apoptosis of MCF-7 cell lines were analyzed; The model of MCF-7 metastatic tumor in nude mice was established and divided into a control group, BMSC group, IL-12 group and a combined group. Intratumoral was injected every 3 d, for 3 times in each group. The nude mice were killed after 15 d, and the tumor and spleen weight of nude mice were compared, χ2 test, t test and variance analysis were used for statistical analysis. Results BMSC conditioned medium inhibited the proliferation of MCF-7 cells, and the inhibition effect was increased [24 h (13.42±1.93)%, 48 h (16.83±1.77)%, 72 h (20.21±2.01)%, F = 6.271, P = 0.000] with the prolongation of action time. The treatment of MCF-7 cells by BMSC conditioned medium promoted apoptosis of MCF- 7 cells effectively, and with the prolongation of action time, the apoptosis rate was increased by [24 h (10.82±2.18)%, 48 h (18.73±2.95)%,72 h (28.15±3.52)%, F = 9.215, P = 0.000]. The tumor volume of the nude mice was compared in the control group [1 d (124.12±9.28) mm3, 3 d (582.41±17.28) mm3, 7 d (983.42±42.10) mm3, 15 d (793.46±109.38) mm3], BMSC group [1 d (132.61±12.41) mm3, 3 d (378.46±23.08) mm3, 7 d (542.61±58.49) mm3, 15 d (329.48±47.51) mm3], IL-12 group [1 d (119.85±13.10) mm3, 3 d (322.75±26.49) mm3, 7 d (518.37±67.54) mm3, 15 d (302.17±68.53) mm3], and the combined group [1 d (123.41±8.94) mm3, 3 d (217.85±24.03) mm3, 7 d (318.29±47.32) mm3, 15 d (189.27±37.58) mm3], the difference was statistically significant (F = 10.821, P < 0.001). The spleen index in BMSC group (7.58 ±1.21), IL-12 group (7.63 ± 1.09) and the combined group (10.03 ± 1.52) were significantly higher than those of the control group (5.37 ± 0.89), and the spleen mass of the nude mice was the highest(F = 13.411, P = 0.000). Conclusion BMSC has a significant inhibitory effect on MCF-7 tumor proliferation in vivo and in vitro. Combined use of pcDNA6/IL-12 has a significant synergistic effect on the inhibition of MCF-7 metastasis in nude mice. Key words: IL-12; Bone marrow mesenchymal stem cells; Human breast cancer cells; Metastatic tumor; Nude mice