血管形成抑制剂3TSR对胰腺癌的治疗作用  

The in vitro and in vivo therapeutic effects of 3TSR on pancreatic cancer cells

作　　者：朱少俊[1] 金洲祥[1] 张雪峰[2] 章小平[2] 董磊[3] 徐鲁白[1] 

机构地区：[1]浙江温州医学院附属第二医院普通外科,325027 [2]美国哈佛医学院Beth Isreal Deaconess医学中心外科系 [3]温州医学院病理学教研室

出　　处：《中华实验外科杂志》2006年第10期1231-1233,i0002,F0003,共5页Chinese Journal of Experimental Surgery

基　　金：浙江省教育厅自然科学基金(20051188)

摘　　要：目的探讨应用血管形成抑制剂3TSR治疗胰腺癌的疗效。方法在体外培养条件下观察3TSR(1μmol/L)、键择(Gem,1μmol/L)和3TSR+Gem(1μmol/L 3TSR,1μmol/L Gem)对胰腺癌细胞增殖和凋亡的影响。24只免疫缺陷雌鼠胰腺原位接种胰腺癌细胞后,随机分为4组,分别腹腔注射生理盐水(0．2 ml),3TSR(3mg/kg体重)、Gem(150mg/kg体重)和3TSR+Gem(3mg/kg体重3TSR,150mg/kg体重Gem),连续3周后,观察肿瘤体积、肿瘤坏死面积、肿瘤微血管。结果体外培养时3TSR对胰腺癌细胞无增殖抑制及诱导凋亡的作用,3TSR+Gem在体外无协同作用。体内实验时3TSR组、Gem组和3TSR+Gem组肿瘤体积较对照组明显降低；3TSR治疗组肿瘤坏死面积百分比为(53．46±3．23)%,较对照组扩大94．5%；Gem组肿瘤坏死面积百分比明显减小,为(6．75±1．60)%,但3TSR+Gem组肿瘤坏死面积百分比较单纯Gem治疗组明显增加；3个处理组肿瘤平均微血管数分别为31．8±10．9、47．0±17．0、36．9±8．3；微血管面积分别为(289．3±128．7)、(408．7±185．3)、(278．4±150．3)μm^2；微血管密度(3．4±0．9)%、(6．0±1．7)%、(3．7±1．3)%,均显著低于对照组(P＜0．05)。结论3TSR能抑制肿瘤新生血管形成,具有显著减少肿瘤体积、肿瘤血管和增加肿瘤细胞坏死的作用,但与化疗药物Gem合用没有明显提高胰腺癌的治疗效果。Objective To investigate the anti-tumor efficacy of angiogenic inhibitor 3TSR on pancreatic cancer cells. Methods Effects of 3TSR （1 μmol/L）, Gemcitabine （Gem, 1μmol/I,） and 3TSR ＋ Gem （1 μmol/L 3TSR, 1 μmol/L Gem） on the proliferation and apoptosis of pancreatic cancer in vitro was observed, respectively. An orthotopic pancreatic cancer model in nude mice was established. Twenty-four nude mice were randomized into 4 groups：control group,3TSR group, Gem group and 3TSR plus Gem group. All animals were treated for consecutively 3 weeks. The changes of tumor volume, the percentage of tumor necrotic area and tumor microvessels were compared among the groups. Results 3TSR could not inhibit cell proliferation and induce apoptosis in pancreatic cancer ceils in vitro. The combination of 3TSR and Gem had no synergistic effects. In vivo studies showed that tumor volume, com- pared with control group,was reduced dramatically in 3TSR,Gem and 3TSR plus Gem groups. The percentage of tumor necrotic area in 3TSR group was （53.46 ± 3.23） % and almost doubled when compared with the control. Gem reduced the percentage of tumor necrotic area to （6.75 ± 1.60） %. But the combination with 3TSR and Gem increased the percentage of tumor necrosis significantly. Average microvessel number in 3TSR,Gem and 3TSR plus Gem group was （31.8 ± 10.9）, （47.0 ± 17.0） and （36.9±8.3） respectively, average microvessel was （ 289.3 ± 128.7） μm2, （408.7 ± 185.3 ） μm^2 and （ 278.4 ± 150.3 ） μm^2 respectively;and average microvessel density was （3.4 ± 0.9） %, （6.0 ± 1.7） % and （3.7 ± 1.3 ） % respectively. In these 3 treated groups microvessel indxes were significantly lower than those in the control group,and among these 3 treated groups the microvessel indexes in the two groups with 3TSR were much lower than those in Gem group. Conclusion 3TSR inhibits tumor angiogenesis,remarkably reduces tumor volume and average microvessel and increases tumor necrosis but there is no synergisti

关 键 词：胰腺癌 血管形成 治疗 

分 类 号：R735.9[医药卫生—肿瘤]