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目的:探讨血管生成抑制剂Canstatin与细胞毒药物5-FU联合应用治疗胰腺癌的效果,以期探索胰腺癌治疗新途径.方法:胰腺癌SW1990细胞(1×107/只)注射到32只裸鼠皮下,建立胰腺癌皮下移植瘤模型.当肿瘤长至2-3mm时,随机分4组,即PBS(0.3mL/d)对照组、5-FU(12.5mg/(kg·d)×5d)治疗组、Canstatin(10mg/(kg·d)×3wk)治疗组、及5-FU[12.5mg/(kg·d)×5d]+Canstatin[10mg/(kg·d)×3wk)]联合治疗组,给药途径均为ip.治疗期间,定期用圆规和游标卡尺测量皮下移植瘤大小.疗程结束时,取下瘤体,常规病理切片,观察药物毒性反应,CD34免疫组化染色,检测肿瘤内微血管密度(MVD).结果:Canstatin治疗组移植瘤体积从第10天起显著小于对照组(P<0.01),5-FU治疗组第7天起就显著小于对照组(P<0.05),而联合治疗组自第3天起,移植瘤体积就显著小于对照组(P<0.05).疗程结束时,联合治疗组小鼠移植瘤体积显著小于其余各组(P<0.01),抑瘤率最高,达83.2%.治疗期间,各实验组未观察到明显毒性反应.免疫组化染色显示,Canstatin组(25.2±3.7)和联合治疗组(22.0±4.8)治疗小鼠肿瘤组织内MVD显著低于对照组(36.8±9.4)和5-FU治疗组(31.6±4.0)(P<0.05),而5-FU治疗组与对照组间无显著差异.结论:重组人Canstatin蛋白能有效抑制人胰腺癌生长,无明显副作用,作用机制是抑制肿瘤新血管形成,与细胞毒药物联合使用,具有协同作用,为胰腺癌治疗提供了新的有力的治疗方法.
To explore the therapeutic effect of Canstatin combined with cytotoxic drug 5-FU on pancreatic cancer in order to explore a new therapeutic approach for pancreatic cancer.Methods: Thirty-two pancreatic cancer cells were injected into SW1990 cells (1 × 107 / mouse) Subcutaneously, a subcutaneous xenograft model of pancreatic cancer was established.When the tumor grew to 2-3 mm in length, the mice were randomly divided into 4 groups: PBS (0.3 mL / d), 5-FU (12.5 mg / (kg xd) (10mg / (kg · d) × 3wk) and 5-FU [12.5mg / (kg · d) × 5d] + Canstatin [10mg / (kg · d) × 3wk) Group, route of administration are ip. During treatment, the size of subcutaneous xenograft was measured regularly with compasses and vernier calipers.At the end of the treatment, the tumor was removed and routine pathological sections were observed to observe the toxicity of drugs and CD34 immunohistochemical staining Microvessel density (MVD) was measured.Results: The volume of tumor in Canstatin treated group was significantly lower than that in control group from the 10th day (P <0.01), and was significantly smaller in the 5-FU treated group than that in the control group on the 7th day (P <0.05) The volume of transplanted tumor in the combination therapy group was significantly smaller than that in the control group (P <0.05), and the tumor volume in the combination therapy group was significantly smaller than that in the other groups (P <0.01) , Up to 83.2% .There was no obvious toxic reaction in each experimental group during the treatment.Immunohistochemical staining showed that MVD in Canstatin group (25.2 ± 3.7) and combination therapy group (22.0 ± 4.8) was significantly lower than that in the treatment group (36.8 ± 9.4) and 5-FU treatment group (31.6 ± 4.0) (P <0.05), but there was no significant difference between 5-FU treatment group and control group.Conclusion: Recombinant human Canstatin protein can effectively inhibit human pancreatic cancer Growth, no obvious side effects, the mechanism of action is to inhibit tumor neovascularization, combined with the use of cytotoxic drugs, has a synergistic effect, provides a new powerful treatment for pancreatic cancer treatment.