南方医科大学学报

南方医科大学学报 ›› 2015, Vol. 35 ›› Issue (02): 223-.

• • 上一篇    下一篇

高强度聚焦超声抑制小鼠黑色素瘤细胞B16-F10在体内的转移

李欢，袁世梅，杨敏，段亮，王海燕，查何，李雪茹，孙晖，翁亚光，罗进勇，何通川，李崇雁，王嫣，李发琪，王志彪，周兰   

  • 出版日期:2015-02-20 发布日期:2015-02-20

High-intensity focused ultrasound inhibits tumor metastasis in a melanoma-bearing
mouse model

  • Online:2015-02-20 Published:2015-02-20

HTML

PDF

2246

摘要： 目的在黑色素瘤的小鼠模型上，探讨高强度聚焦超声（HIFU）处理对黑色素瘤细胞体内转移的影响。方法皮下注射小
鼠黑色素瘤细胞B16-F10以构建小鼠黑色素瘤皮下移植瘤模型；待肿瘤最长径长至7~10 mm时进行HIFU处理，并设置实验对
照组（荷瘤鼠辐照HIFU但保持治疗头功率源开关关闭，即假照组）；治疗后每3 d测量肿瘤长径和短径，共观察3周，绘制肿瘤曲
线，统计生存率和转移率，并通过实时荧光定量PCR测定血液中黑色素瘤细胞3个标志物的相对表达量以监测血液中循环黑色
素瘤细胞的数量，它们分别是黑色素瘤相关抗原A3（MAGE-A3）、T细胞1识别的黑色素瘤抗原（MART1）以及同源转化成对框
基因转录因子PAX3)；在HIFU治疗后14 d，通过尾静脉注射再次移植B16-F10细胞，观测其肺转移率。结果（1）各自的中位生
存时间及95 %可信区间（CI）：假照组分别为19.00 d和17.14~20.86 d，HIFU组则分别为26.00d和24.76~27.25 d，生存率差异显
著（P<0.01）；从治疗后第20天起，两组小鼠的肿瘤体积差异明显，从HIFU处理后第20天开始，包括处理后第23、26天，辐照组
小鼠肿瘤体积明显小于假照组（P<0.05）；（2）实时荧光定量PCR结果显示HIFU组小鼠在治疗后第7天的MAGE-A3、MART1
和PAX3三个指标都明显低于假照组（P<0.05），在治疗后第14天其MAGE-A3的表达量仍然明显低于假照组（P<0.05）；（3）在
HIFU治疗后14 d通过尾静脉再次移植相同肿瘤细胞，HIFU组肺转移灶的数量明显低于假照组（P<0.05），肿瘤转移抑制率为
42.4%。结论HIFU处理能够抑制黑色素瘤细胞在体内转移的发生，其机制可能涉及减少肿瘤细胞从原发灶的脱落和瘤细胞在
肺部的定植能力。

Abstract: Objective To investigate the effect of high-intensity focused ultrasound (HIFU) on tumor metastasis in mouse model
bearing melanoma xenograft. Methods Mice bearing murine melanoma B16-F10 cell xenograft were randomized for
sham-HIFU or HIFU exposure when the tumors grew to a maximum diameter of 7-10 mm, and the tumor size was measured
every 3 days. The cumulative survival rate of the mice and tumor metastasis rate were calculated, and the circulating
melanoma cells were detected using qRT-PCR. At 14 days after HIFU treatment, B16-F10 cells were retransplanted via the tail
vein and the pulmonary metastatic nodules were counted. Results The median survival time of the mice was 19.00 days (95 %
CI 17.14-20.86 days) in the sham group and 26.00 days (95%CI 24.76-27.25 days) in HIFU group. The cumulative survival rate
in the HIFU group was significantly higher than that in sham-HIFU group (P<0.01), and the tumor size was significantly
smaller in HIFU group at 20, 23, and 26 days after HIFU treatment (P<0.05). Compared with the sham-HIFU group, HIFU
group had significantly lower levels of MAGE-A3, MART1 and PAX3 at 7 days after HIFU (P<0.05) with still lower MAGE-A3
level at 14 days (P<0.05). HIFU group showed a significantly smaller number of pulmonary metastatic nodules following
tumor cell retransplantation than in sham-HIFU group (P<0.01) with a metastasis inhibition rate of 42.4%. Conclusion HIFU
treatment can inhibit tumor metastasis in melanoma-bearing mice possibly by reducing tumor cell detachment from the
primary tumor site and suppressing colonization of the circulating melanoma cells.