Objective        To determine the damaging effect of picosecond pulse electric field (psPEF) on the nude mice model of cervical cancer and investigate the underlying possible mechanism.       Methods        Nude rat xenograft model of cervical cancer was established by implanting HeLa cells in the back of the animals. Among the 36 rats with tumor mass over 1 cm in size

24 were randomly chosen and then divided into control group

and groups in 6

12 and 24 h after treatment. Treatment group were treated under a psPEF of pulse number 2 000

pulse width 800 ps

voltage 70 kV

and frequency 3 Hz

and control group received no such treatment. After the tumor mass were harvested at the corresponding time points

tumor morphology was observed by using HE staining and transmission electron microscopy (TEM)

cell apoptosis was determined by TUNEL. Mitochondrial transmembrane potential was assessed by Jc-1 staining on laser scanning confocal microscopy (LSCM). The activity of caspase-3

8

9 and 12 were detected by activity assay kit. Another 12 animal model were randomly divided into the treatment group and control group

the tumor volume we measured every 3 days after psPEF treatment and the relative tumor proliferation rate was calculated.       Results        Tumor tissue occurred necrosis at different degrees after treatment

and the tissue from 24 h after treatment was heaviest. Electron microscopy showed apoptotic bodies in the tumor cells

most commonly in the cells from 12 h after treatment. The apoptotic rate was significantly higher in all the treatment groups than the control group

and the 12 h group was significantly greater than the other groups (P0.01). Mitochondrial membrane potential was decreased with the extension of treatment time. The activities of proteins caspase-3 and -12 was significantly higher in the 12 h group than the other groups

and those of caspase-8 and -9 had no significant difference among the treatment groups and control group. There were significant differences in tumor volume between the control group and the groups in 3

6 and 9 d after psPEF treatment

and the relative tumor growth rate was 76.87%

71.00%

and 68.87% respectively for the above 3 time points.       Conclusion        PsPEF can be used on cervical cancer xenograft model

and leads to necrosis and cell apoptosis in tumor tissue

showing inhibitory effect on tumor early growth.