Abstract: Objective The purpose of this experiment was to explore inhibitory effects of Fe₃O₄ nanometer magnetic carrier-induced hyperthermia under extremely low frequency electromagnetic fields (ELF-EMF) on implanted tumors in nude mice Methods A tumor model in nude mouse was established by implanted Bel-7402 liver cancer cells and the tumor-bearing nude mice were randomly divide into control, intervened in magnetic field and intervened in nano magnetic fluid under extremely low frequency electromagnetic fields (ELF-EMF), with 20 mice in each. The animals in experiment received intratumor injection of PEG-PEI / Fe₃O₄ 0.1 ml under 0.7 mT magnetic field for 1 hour, twice a day and continued for 15 days. Serum VEGF, HIF-1α, sIL-2R and MMP-2 levels were detected. Results At day seven and fifteen, the tumor volume in nude mice in nano-magnetic fluid-treated group were (113.5±12.2) mm³ and (97.6±9.7) mm³, significantly smaller than in control group or in magnetic field-treated group [(204.6±13.5) mm³ and (452.8±16.5) mm³, or (146.7±13.4) mm³ and (118.8±13.6) mm³, respectively, P < 0.05]; the tumor weight was (0.8±0.1) g, significantly lower than [(2.0±0.2) g or (1.4±0.1) g, P <0.05] in control or in magnetic field-treated group, and the tumor inhibition rates in magnetic field and nanomagnetic fluid group were 26.2% and 56.9%, respectively (P < 0.05); serum VEGF, HIF-1α, sIL-2R, and MMP-2 were (127.4±14.2)pg/ml,(32.4±5.2)ng/L,(227.5±23.7)ng/L and (132.4±15.7)pg/ml], all significantly lower [(294.6±18.6)pg/ml,(107.5±12.7)ng/L,(823.6±38.7)ng/L and (453.6±25.4)pg/ml,respectively, P <0.05] in control or [(215.7±14.3)pg/ml,(72.4.±7.5)ng/L,(426.3±24.4)ng/L and (214.3.±18.4)pg/ml,respectively, P <0.05] in magnetic field; the histopathological examination showed the tumor cells in the control group grew vigorously, with large dense cells and disordered arrangement, the tumor cell growth in the magnetic field was restricted, sparsely arranged, with increased interstitial tissues, and the tumor in the nano-magnetic fluid group showed wide necrosis, with reduced tumor cells. Conclusion Fe₃O₄ nano-magnetic fluid intervention under ELF-EMF has a good inhibition effects on angiogenesis in implanted tumor in nude mouse, which could inhibit tumor growth and liver cancer cell proliferation, and promote apoptosis of the liver cancer cells.

Key words: Hepatoma cell lines, Extremely low frequency electromagnetic fields, Nano-magnetic fluid, Nuke mice