survivin反义寡核苷酸对胰腺癌荷瘤裸鼠的治疗作用  

Therapeutic effects of survivin antisense oligonucleoUde on nude mice bearing human pancreatic carcinoma xenograft

作　　者：刘江伟[1] 张永久[1] 皇甫清风[2] 李开宗[3] 张东[1] 雷涛[1] 

机构地区：[1]兰州军区乌鲁木齐总医院普外科,新疆维吾尔自治区乌鲁木齐市830000 [2]兰州军区乌鲁木齐总医院干部病房,新疆维吾尔自治区乌鲁木齐市830000 [3]第四军医大学西京医院肝胆外科,陕西省西安市710032

出　　处：《世界华人消化杂志》2006年第29期2838-2843,共6页World Chinese Journal of Digestology

摘　　要：目的：探讨survivin反义寡核苷酸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,采用瘤内注射方式,每只注射survivin反义寡核苷酸(ASODN)40g/200L,对裸鼠进行干预治疗．观测裸鼠肿瘤生长情况及瘤体质量、病理形态：应用RT-PCR检测肿瘤的survivin mRNA变化：应用caspase-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20d后,survivin ASODN治疗组的平均体积(427．34±12．44mm^3)明显小于对照组(703．56±12．51mm^3)和正义组(687．59±12．44mm^3)(P＜0．01)；治疗组瘤重(0．57±0．06g)也显著低于对照组(1．16±0．12g)和正义组(1．07±0．10g)(P＜0．01),抑瘤率为50．86％．survivin ASODN治疗组survivin mRNA与对照组和正义组相比降低了约50％：survivin ASODN治疗组肿瘤的caspase-3相对活性明显高于对照组和正义组(0．040±0．018 vs 0．006±0．001,0．007±0．002,P＜0．01)：survivin ASODN治疗组的PI(28．33±2．16)明显低于对照组(35．17±3．71)和正义组(34．33±3．27)(P＜0．01)；sHrvivin ASODN组MVD(15．50±3．08)明显低于对照组(21．33±2．94)和正义组(20．67±2．16)(P＜0．01)；而对照组和正义组PI和MVD均无显著性差异(P＜0．05)．结论：survivin ASODN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．AIM： To investigate the therapeutic effects of survivin antisense oligonucleotide （ASODN） on nude mice bearing human pancreatic carcinoma xenograft. METHODS： The nude mouse model of pancreatic cancer was established using human pancreatic cancer cell line BxPC-3. The mice bearing tumor were intratumorally injected with survivin ASODN （40 g/200 L per mouse）. The tumor size and volume were measured before and after injection. The pathological changes of tumor tissues were observed. The expression level of survivin mRNA was measured by reverse transcription-polymerase chain reaction （RT-PCR）, and the activity of caspase-3 was evaluated using a caspase-3 assay kit. The expression of proliferating cell nuclear antigen （PCNA） and microvessel density （MVD） were detected by immunohistochemistry. RESULTS： Twenty days after injection, the tumor volume and weight were significantly decreased in survivin ASODN group as compared with those in the control and SODN group （427.34 ± 12.44 mm^3 vs 703.56 ± 12.51, 687.59 ± 12.44 mm^3, P 〈 0.01; 0.57 ± 0.06 g vs 1.16 ± 0.12, 1.07 ± 0.10 g, P 〈 0.01）, and the tumor inhibition rate was 50.86%. The expression of survivin mRNA was decreased by 50%, while the caspase-3 activity was significantly higher in survivin ASODN group than that in the control and SODN group （0.040 ± 0.018 vs 0.006 ± 0.001, 0.007 ± 0.002, P 〈 0.01）. The expression of PCNA and MVD were significantly lower in survivin ASODN group than those in the control and SODN group （28.33 ± 2.16 vs 35.17 ± 3.71, 34.33 ± 3.27, P 〈 0.01; 15.50 ± 3.08 vs 21.33 ± 2.94, 20.67 ± 2.16, P 〈 0.01）. However, both expression of PCNA and MVD had no significant difference between the control and SODN group （P 〉 0.05）. CONCLUSION： Survivin ASODN can inhibit the growth of human pancreatic carcinoma xenograft in nude mouse through activating caspase-3 to induce apoptosis, and suppressing the proliferation of pancreatic cancer cells as well as the angiogenesis of carcino

关 键 词：胰腺癌 SURVIVIN 反义寡核苷酸 裸鼠 

分 类 号：R735.9[医药卫生—肿瘤]