Abstract: ABSTRACT Objective：To investigate the effect of nanosecond pulsed electric fields(nsPEF)on human melanoma A375 cell xenograft in nude mice and its possible mechanisms. Methods：Nude mice models were randomly divided into long-term treatment group for observing tumor growth and survival time （ ten mice every group），and short-term treatment group (includes 2h group、4d group and control group,4、6 and 6 mice ,respectively) exposed to the 40kV/cm, 200ns, 1HZ, 1000 pulses .Tumor morphology was observed with HE staining; The cell apoptosis was detected by DNA agarose gel electrophoresis and terminaI deoxynucleotidyl transferase-mediated dUTP nick end-labeling (TUNEL) assay; The expression of Bax and Bcl-2 protein was detected by Western blot and SP immunohistochemistry. Results: Tumor turned grey without bleeding spots minutes after long-term treatment,the tumor volume was significantly smaller in treatment group than in control group ( P<0.01),the mean survival time was significantly longer in treatment group()than in control group()(P<0.01).Cell necrosis was found in 4d group;DNA ladder was observed in 4d group;the apoptosis rate of tumor cells was significantly higher in 4d group than control group ( P<0.01);the expression of Bax was significantly higher in 4d group than in control group (P<0.01); the expression of Bcl-2 was significantly lower in 4d group than in control group after short-term treatment( P<0.01). Conclusion: nsPEF may cause melanomas complete remission without recurrence by inducing cell apoptosis under the Bax and Bcl-2 gene regulation mechanism .

Key words: [KEY WORDS] Nanosecond pulsed electric fields(nsPEF), Human melanoma, Apoptosis, Bax, Bcl-2