高强度聚焦超声联合赛来昔布治疗胰腺癌裸鼠移植瘤的实验研究

目的研究高强度聚焦超声（HIFU）联合选择性环氧合酶-2抑制剂赛来昔布对胰腺癌裸鼠移植瘤生长的影响。方法40只裸鼠建立胰腺癌裸鼠移植瘤模型，随机分对照组、HIFU组、赛来昔布组及联合组共观察40d，研究各处理因素对移植瘤生长的影响。观察4组移植瘤组织病理学变化，RT-PCR检测bcl-2、bax及HSP70的表达，免疫组化检测HSP70的表达。结果联合组移植瘤平均体积最小，赛来昔布组、HIFU组、联合组抑瘤率分别为81．3％、93％、99．7％。病理示HIFU组和联合组中见大片凝固性坏死，HIFU组可见残留癌细胞小岛而联合组未见。FT-PCR示bcl-2在各组中均表达极弱；bax在HIFU组、赛来昔布组及联合组中表达均上调；HSP70以联合组表达上调最明显。免疫组化示HIFU组、联合组HSP70呈强阳性表达。结论HIFU与赛来昔布联合对胰腺癌裸鼠移植瘤的治疗可起到协同作用。HIFU不仅可以直接杀灭肿瘤细胞，而且可以通过上调bax的表达诱导肿瘤细胞凋亡；通过上调HSP70的表达激发机体的免疫反应进一步抑制肿瘤生长。

High-intensity ultrasound in combination with celecoxib for treatment of implanted pancreatic carcinoma in nude mice

Objective To investigate the tumoricidal effects of high-intensity ultrasound (HIFU) in combination with celecoxib, a kind of selective cyclooxygenase-2 inhibitor, on the implanted pancreatic carcinoma in nude mice. Methods The model of pancreatic xenograft carcinoma was established in 40 nude mice by inoculating SW1990 cells. The 40 nude mice were then divided into the control group, HIFU group, celecoxib group and combination group. The growth of the implanted carcinoma was observed for 40 d and pathological changes determined in all the 4 groups. RT-PCR was used to determine the expression of bcl-2, bax and HSP70. The expression of HSP70 in the implanted carcinoma was detected with immunohistochemistry. Results Compared with other 3 groups, the combination group had the smallest average tumor size and the highest inhibition ratio of the implanted carcinoma. There were large coagulation and necrosis areas in HIFU and combination group and residual survival tumor cells could also be seen in HIFU group. Bax expression was up-regulated in all the treated groups but that of bcl-2 had no significant change. The expression of HSP70 markedly increased in HIFU and combination group. Similar trend of HSP70 expression was shown by immunohistochemical staining. Conclusions HIFU in combination with celecoxib has a synergistic effect on implanted pancreatic carcinoma in nude mice. HIFU can not only directly destroy tumor cells but also up-regulate bax and HSP70 expression to induce tumor cell apoptosis and initiate body immune defense.