Objective:To explore the impact of low-frequency ultrasound combing microbubbles mediated microvessel disruption on radiofrequency ablation in treating nude mice with human prostate cancer xenografts.Methods:Tumor-bearing nude mice were randomly divided into three groups:USMB + BPA group was treated with low-frequency ultrasound combing microbubbles immediately followed by radiofrequency ablation,RFA group was treated with radiofrequency ablation alone and Control group was not treated.1 day,4 days and 7 days after treatment in the two treatment groups,ablation volume and ablation rate was compared between RFA group and USMB+ RFA group,and tumor volumes,HE staining,apoptotic index,proliferative index and microvessel density was compared in the three groups.Results;USMB + RFA group produced measurable tumor volume reduction,decreased from 76.96 ± 23.09 mm3 tol5.19 ± 7.91 mm3;in RFA group tumor,tumor volumes increased from 98.37 ± 16.23 mm3 to 182.24 ±30.62 mm3;in Control group,tumor volumes increased from 76.01 ± 18.83 mm3 to 205.07 ± 28.16 mm3,the changes in three groups were all significant(all P < 0.05).1 day after treatment,there was no significant difference in tumor volumes in the three groups.4 days after treatment,significant differences in tumor volumes were observed among the three groups(P < 0.05);tumor volumes were reduced by treatment with USMB combined with RFA,while RFA group produced bigger tumor volumes when compared with the controls(p < 0.001 and P= 0.037,respectively).7 days after treatment,the tumor volumes were smaller in USMB + RFA group compared with the other two groups(all P < 0.001).In USMB +RFA group,ablation volumes decreased from 76.96 ±23.09 mm3 tol5.19 ±7.91 mm3,the differences were all significant(all P <0.05);in RFA group,ablation volumes had not changed significantly(all P > 0.05).1 day and 4 days after treatment,larger average volume of ablation lesion was seen in USMB + RFA group than that of RFA group(P = 0.002 for 1 day after treatment,P = 0.022 for 4 days after treatment).Ablation rates were higher in USMB + RFA group compared with RFA group 1 day,4 days and 7 days after treatment(all P<0.001).HE staining showed that,large areas of coagulative necrosis were existed in USMB + RFA group and RFA group,while there was small focal areas of necrosis could be seen in Control group occasionally;necrotic areas could reached tumor capsules in 6 tumors in USMB + RFA group,while in RFA group,all necrotic areas had not reached the capsules.There were less apoptotic cells and more proliferative cells of RFA group than Control group 1 day,4 days and 7 days after treatment(all P <0.05).Apoptotic index of USMB + RFA group was lower than that of Control group and higher than that of RFA group 1 day after treatment(P=0.034 and P=0.016 respectively).Proliferative index of USMB + RFA group was higher than that of Control group and lower than that of RFA group 4 days and7 days after treatment(all P <0.05).There was no significant differences in microvessel density among the three groups throughout the experiment.Conclusions:Using low-frequency ultrasound combing microbubbles before radiofrequency ablation could produce larger volumes of ablation than radiofrequency ablation alone,promote apoptosis and inhibit proliferation in residual carcinoma cells after radiofrequency ablation.