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[Effects of high-intensity focused ultrasound on apoptosis-associated gene expression in xenografts with human pancreatic cancer].

Objective: To identify the expression of apoptosis-associated genes of high- intensity focused ultrasound(HIFU) in xenograft with human pancreatic cancer. Methods: Mice implated with human pancreatic cancer cells (YY-1) were divided into HIFU group or control group. Tumor cell apoptosis was verified by TUNEL. The expression of the apoptosis-associated genes was analyzed by Agilent Human Gene Expression. Selected genes was validated by quantitative real-time PCR(RT-PCR)and Western blot. Results: The rate of tumor cell apoptosis in HIFU group was higher than that of control group at 7, 14 days after HIFU treatment ((63.6%±15.2%)vs (19.0%±2.4%), P<0.01)and ((41.4%±7.3%)vs(18.0%±2.4%), P<0.01). Gene expression profiling revealed a total of 69 differentially expressed genes in related to apoptosis pathway, among which 44 genes were up-regulated, and 25 genes down-regulated. The RT-PCR results of selected 4 genes were consistent with those of gene expression profiling. The results of Western blot analysis at 7, 14 days after HIFU treatment showed that the expressions level of Bax protein in HIFU group was greater that of in control group ((0.39±0.11)vs (0.20±0.09), P<0.05)and ((0.46±0.12)vs(0.24±0.10), P<0.05), while the expressions level of Bcl-2 protein in HIFU group was lower than that of in control group ((0.68±0.14)vs(1.56±0.21), P<0.05)and((0.51±0.16)vs(1.57±0.22), P<0.05). Conclusions: HIFU could induce apoptosis and results in dramatic changes in gene expression, indicating that multiple pathways are involved. Although intrinsic pathway might be predominantly involved in HIFU-elicited apoptosis, further research is needed to clarify the detailed mechanisms.