塞来昔布联合survivin反义寡核苷酸对胰腺癌荷瘤裸鼠的治疗作用  

Therapeutic effects of celecoxib in combination with survivin antisense oligonucleotides on nude mice bearing human pancreatic carcinoma xenograft

作　　者：刘江伟[1] 李开宗[2] 窦科峰[2] 张东辉[1] 许永华[1] 张东[1] 冯德元[1] 杨自更[1] 

机构地区：[1]解放军兰州军区乌鲁木齐总医院肝胆外科,新疆乌鲁木齐830000 [2]第四军医大学西京医院肝胆外科,陕西西安710032

出　　处：《现代生物医学进展》2008年第11期2034-2037,共4页Progress in Modern Biomedicine

摘　　要：目的:探讨环氧化酶-2(COX-2)抑制剂塞来昔布和survivin反义寡核苷酸(ASODN)联合作用对胰腺癌荷瘤裸鼠的治疗作用。方法:构建胰腺癌荷瘤裸鼠模型,将成瘤裸鼠随机分为4组:对照组、塞来昔布组(给予1000ppm的塞来昔布饮水)、survivin ASODN组(瘤内注射40μg/200μL的survivin ASODN)、联合组(给予1000ppm的塞来昔布饮水的同时瘤内注射40μg/200μL的survivin ASODN);观测裸鼠肿瘤生长情况并测量不同时间的体积变化,于接种肿瘤的35天处死裸鼠,测瘤体质量,应用cas- pase-3试剂盒检测caspase-3活性,免疫组织化学法检测肿瘤增殖指数(PI)和微血管密度(MVD)。结果:治疗组平均体积均明显低于对照组(491.97±4.62mm^3,427.34±14.62mm^3,300.39±6.59mm^3 vs 703.56±12.51 mm^3,P<0.01),其中联合治疗组体积明显低于塞来昔布组或survivin ASODN组(P<0.01);平均抑瘤率分别为32.26%、50.86%、62.07%。治疗组caspase-3相对活性明显高于对照组(0.026±0.003、0.040±0.018、0.059±0.005 vs 0.006±0.001,P<0.01),其中联合治疗组caspase-3相对活性明显高于塞来昔布组(P<0.01)或survivin ASODN组(P<0.05);治疗组平均PI和MVD均明显低于对照组(P<0.01,或P<0.05),其中联合治疗组平均PI和MVD明显低于塞来昔布组或survivin ASODN组(P<0.01,或P<0.05)。结论:COX-2抑制剂塞来昔布和survivin ASODN联合应用可显著抑制荷胰腺癌裸鼠的肿瘤生长,其作用机制可能是通过共同提高caspase-3活性来诱导细胞凋亡,通过抑制肿瘤细胞的增殖和新生血管的形成来发挥抗肿瘤效应,为胰腺癌的治疗提供了新的思路。Objective：To investigate the therapeutic effects of COX-2 inhibitor celecoxib in combination with survivin antisense oligonucleotide （ASODN）on nude mice bearing human pancreatic cancer xenograft.Methods：The nude mouse model of pancreatic cancer was established with human pancreatic cancer cell line BxPC-3.The mice bearing tumor were randomly divided into 4 groups： control group,celecoxib group （provided with water containing 1000ppm celecoxib）,survivin ASODN group （intratumorally injected with survivin ASODN at the concentration of 40μg/200μL per mouse each time）,combination group （provided with water containing 1000 ppm celecoxib and at the same time intratumorally injected with survivin ASODN at the concentration of 40μg/200μL per mouse each time）.The tumor size and volume were measured at different time,the nude mice were sacrificed 35 days after the inoculated began. The weight of each tumor was weighed,the caspase-3 activity was evaluated using a caspase-3 assay kit;the expression of proliferating cell nuclear antigen（PCNA）and microvessel density（MVD）were observed using immunohistochemistry.Results：The tumor volumes in the three experimental groups were significantly smaller than that in the control group （491.97±4.62mm^3,427.34±14.62mm^3,300.39±6.59 mm^3 vs 703.56±12.51 mm^3,P〈0.01）,the tumor volume of the combinition group was significantly smaller than that of the celecoxib group or the survivin ASODN alone.The tumor inhibition rate of the three experimental groups were 32.26%, 50.86%,62.07%,respectively.The caspase-3 activities were significantly higher in the three experimental groups than that in in the con- trol group （0.026±0.003,0.040±0.018,0.059±0.005 vs 0.006±0.001,P〈0.01）.The caspase-3 activities of the combinition group were significantly higher than that in the celecoxib group（P〈0.01）or the survivin ASODN alone（P〈0.05）.The expressions of PCNA and MVD were significantly lower in the three experimental groups than that in the con

关 键 词：胰腺癌 环氧化酶-2 塞来昔布 survivin 反义寡核苷酸 裸鼠 

分 类 号：R657.3[医药卫生—外科学]