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目的:探讨通过Matrigel与肿瘤细胞混合接种的方法构建裸鼠人食管癌Matrigel移植瘤模型的可能性,进一步研究抗肿瘤制剂PI-88对于人食管癌Matrigel移植瘤生长及血管新生的影响。方法:将食管鳞癌细胞株TE-13悬液与Matrigel胶混合,接种8只裸鼠,构建人食管癌TE-13细胞Matrigel裸鼠移植瘤模型,将其随机分为PI-88治疗组和对照组。治疗组按照20 mg/kg剂量皮下注射PI-88,1次/d(PI-88配成1 mg/ml溶液);对照组按照20 ml/kg注射生理盐水,1次/d,均连续给药2周。第2、6、10、14天记录裸鼠肿瘤体积,第15天进行增强CT扫描观察肿瘤区域显影情况。免疫组化染色观察肿瘤组织中乙酰肝素酶(heparanase,HPSE)和血管内皮生长因子(vascular endothelial growth factor,VEGF)的表达。结果:8只裸鼠均在接种当天形成移植瘤,成功构建TE-13细胞Matrigel裸鼠移植瘤模型。PI-88治疗第14天时,治疗组肿瘤体积明显小于对照组[(70.25±6.85)vs(143.13±17.18)mm3,P<0.05]。治疗第15天时,治疗组肿瘤区域CT值明显低于对照组(15.18±0.91vs 19.23±2.03,P<0.05)。治疗组肿瘤组织内HPSE与VEGF表达阳性细胞数显著低于对照组[HPSE:(28.70±6.39)vs(87.55±22.03)个,t=11.472,P<0.01;VEGF:(47.10±8.18)vs(94.40±14.47)个,t=12.727,P<0.01]。结论:Matrigel胶混合食管癌细胞接种裸鼠制备移植瘤方法可行,PI-88能够抑制人食管癌TE-13细胞Matrigel裸鼠移植瘤生长及血管新生,其作用机制可能与PI-88抑制移植瘤组织中HPSE和VEGF表达有关。
OBJECTIVE: To investigate the possibility of establishing a Matrigel xenograft model of human esophageal cancer in nude mice by inoculation with Matrigel and tumor cells, and further investigate the effect of antitumor agent PI-88 on the growth and angiogenesis of human esophageal cancer Matrigel xenografts. Methods: The esophageal squamous carcinoma cell line TE-13 suspension was mixed with Matrigel and inoculated with 8 nude mice to construct the transplanted tumor model of human esophageal carcinoma TE-13 cell line Matrigel in nude mice. The model was randomly divided into PI-88 treatment group and Control group. In the treatment group, PI-88 was injected subcutaneously at a dose of 20 mg / kg once a day for 1 mg / ml and the control group was given saline at a rate of 20 ml / kg once a day for Medicine for 2 weeks. On the 2nd, 6th, 10th and 14th days, the tumor volume of the nude mice was recorded. On the 15th day, the enhanced CT scan was performed to observe the tumor area development. Immunohistochemical staining was used to observe the expression of heparanase (HPSE) and vascular endothelial growth factor (VEGF) in tumor tissue. Results: All of the 8 nude mice formed xenografts on the day of inoculation, and successfully constructed the transplanted tumor model of TE-13 cells in nude mice. On the 14th day after PI-88 treatment, the tumor volume in the treatment group was significantly smaller than that in the control group [(70.25 ± 6.85) vs (143.13 ± 17.18) mm3, P <0.05]. On the 15th day of treatment, the CT value of the tumor area in the treatment group was significantly lower than that in the control group (15.18 ± 0.91 vs 19.23 ± 2.03, P <0.05). The number of positive cells of HPSE and VEGF in the treatment group was significantly lower than that in the control group [HPSE: (28.70 ± 6.39) vs (87.55 ± 22.03), t = 11.472, P <0.01; VEGF: 47.10 ± 8.18 vs 94.40 ± 14.47), t = 12.727, P <0.01]. Conclusions: Matrigel inoculated with esophageal carcinoma cells in nude mice is feasible. PI-88 can inhibit the growth and angiogenesis of transplanted tumor in nude mice with esophageal cancer TE-13 cells. HPSE tissue and VEGF expression.