[Non-thermal effect of high-intensity focused ultrasound on ultrastructure and apoptosis in rabbit hepatic VX2 tumors].
OBJECTIVE
To observe the micromorphological changes of ultrastructure, apoptosis-related proteins expression and tumor cell apoptosis after ablation with the high-intensity focused ultrasound (HIFU), and to explore the mechanisms responsible for the thermal and non-thermal effect.


METHODS
Forty rabbits with hepatic VX2 tumors were randomly divided into a thermal group (n=20) and a non-thermal group (n=20), and were subjected to HIFU ablation with thermal or non-thermal condition, respectively. Five animals in each group were sacrificed on the 1st, 3rd, 7th or 14th day after the ablation. The changes of ultrastructure, apoptosis-related proteins expression and tumor cell apoptosis were detected.


RESULTS
The results of transmission electron microscope (TEM) revealed more severe injury on tissue and cells in the non-thermal group than that in the thermal group. The changes of apoptosis-related proteins expression and tumor cell apoptosis in transient zone were significantly different in comparison with that in the ablated area or peripheral area between the two groups. The expression of vascular endothelial growth factor (VEGF) was at low level on the 1st and 3rd day and elevated gradually on the 7th and 14th day, with no significant difference (all P>0.05). The expression of caspase-3 reached peak on the 3rd day and decreased on the 7th and 14th day. It was significantly higher in the non-thermal group than that in the thermal group on the 3rd and 7th day (all P<0.05). The expression of NF-κB was elevated from the 3rd day and reached peak on the 7th day while decreased on the 14th day. There was no significant difference at every time point between the 2 groups (all P>0.05). The apoptosis index in the non-thermal group and the thermal group on the 3rd and 7th day were (28.60±1.14)% vs (21.80±1.92)% and (21.00±1.58)% vs (14.80±1.48)%, respectively. It was higher in the non-thermal group than that in the thermal group (both P<0.01).


CONCLUSIONS
Both the thermal and the non-thermal effect of HIFU can induce apoptosis in transient zone, but the latter have a stronger effect.
Department of Radiology, Third Xiangya Hospital, Central South University, Changsha 410013, China.
Song
S
Peng
Department of Ultrasonography, Third Xiangya Hospital, Central South University, Changsha 410013, China.
Wei
W
He
D000818:Animals; D017209:Apoptosis; D053148:Caspase 3 / Q000378:metabolism; D057086:High-Intensity Focused Ultrasound Ablation; D008113:Liver Neoplasms / Q000473:pathology / Q000648:ultrastructure*; D016328:NF-kappa B / Q000378:metabolism; D009374:Neoplasms, Experimental / Q000473:pathology / Q000648:ultrastructure; D011817:Rabbits; D042461:Vascular Endothelial Growth Factor A / Q000378:metabolism
D016328:NF-kappa B; D042461:Vascular Endothelial Growth Factor A; D053148:Caspase 3