Ad-PUMA联合SU5416对裸鼠胰腺癌生长和转移的抑制作用

Inhibitive effects of Ad-PUMA combined SU5416 on pancreatic cancer growth and metastasis in experimental rat

目的:研究重组腺病毒(Ad)-PUMA联合SU5416对裸鼠胰腺癌生长和转移的抑制作用。方法:建立裸鼠胰腺癌AsPC-1细胞株原位移植瘤模型,将胰腺癌裸鼠随机分为4组,于模型的第14天,分别自腹腔注射生理盐水100μL(对照组,n=8)、Ad-PUMA3×108pfu/100μL(PUMA组,n=10)、SU5416制剂16mg/kg(SU5416组,n=9)和Ad-PUMA+SU54163×108pfu/100μL+SU541616mg/kg(联合组,n=10)。治疗2周后处死裸鼠,剖腹测量原位肿瘤瘤重、抑瘤率、肿瘤微血管密度、胰腺癌细胞凋亡指数,同时观察腹膜、肝脏及毗邻脏器转移和腹水情况。结果:对照组、PUMA组、SU5416组、联合组诱发肿瘤瘤重分别为(0.72±0.08)、(0.48±0.06)、(0.52±0.07)、(0.21±0.04)g,抑瘤率分别为0、28%、34%、71%,肿瘤微血管密度分别为21.4±2.7、20.2±2.5、8.3±1.6、3.8±1.0,凋亡指数分别为(2.7±1.8)、(13.7±3.4)、(5.5±3.7)、(20.6±8.6)%,腹膜转移率分别为87%、70%、33%、10%,肝转移率分别为75%、50%、22%、0,联合组与对照组比较差异有统计学意义(P均<0.05)。结论:Ad-PUMA联合SU5416具有协同抗胰腺癌作用。

Objective： To study the inhibitive effects of Ad-PUMA combined angiogenesis inhibitor SU5416 on pancreatic cancer growth and metastasis in athymic mouse. Methods： The pancreatic carcinoma athymic mouse model with AsPC-1 cell strain orthotopic transplantation was established. The mice were randomly divided into 4 groups to receive peritoneal cavity injection at the 14th day separately with ： Normal saline （control,n= 8）, Ad-PUMA 3 × 10^8pfu/100 μL （PUMA group, n = 10）, SU5416 16mg/kg（SU5416 group, n =9） and AdPUMA＋ SU5416 （combined group, n = 10）. Mice were killed after 2 weeks treatment. Tumor weight, inhibition rates, intratumoral microvessel density （MVD） and apoptotic index （AI） were measured, meanwhile, abdominal membrane, liver and adjacent organic metastasis and ascites were observed. Results： Tumor weights were （0.72 ±0.08）g, （0.48 ±0.06）g , （0.52 ±0.07）g, （0.21 ±0.04）g, in 4 groups respectively; the inhibitive rates were 0.28 % ,34% ,71% respectively; the intratumoral microvessel densities （MVD） were 21.4 ± 2.7,20.2 ±2.5,8.3 ± 1.6,3.8 ± 1.0 respectively ; The apoptotic indexes （AI） were （ 2.7 ± 1.8 ） %, （ 13.7 ± 3.4） %, （ 5.5 ±3.7） %, （20.6 ± 8.6） % respectively ; Peritoneal metastasis rates were 87% ,70% ,33%, 10%, and liver metastasis rates were 75% ,50% ,22% ,0 （P 〈0.05）. There was significant difference between combined group and control （P 〈0.05）. Conclusion： Ad-PUMA combined with SU5416 inhibits the pancreas cancer growth and metastasis in mouse.