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\[（70.25±6.85） vs （143.13±17.18） mm3，P<0.05\]。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91 vs 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 create a mouse xenograft model of esophageal squamous cancer by coinjection of tumor cells with matrigel and to determine the anti-tumor and anti-angiogenic effects of PI-88 using this model. Methods: Nude mice were co-injected with human esophageal cancer TE-13 cells and matrigel subcutaneously. They were then randomized to receive subcutaneously physical saline (n=4, 20 ml/\[kg?day\]) as controls and PI-88 (n=4, 20 mg/\[kg?day\]) as test treatment, respectively. At day 2, 6, 10, 14 d after the last dose, contrast enhanced CT scans were performed on the xenograft region and xenograft tumor specimens were collected for analyses of heparanase (HPSE) and vascular endothelial growth factor(VEGF), respectively, by S-P staining and histoimmunological staining. Results: Xenograft tumors were formed on the same day of tumor cell injection in 8 mice. On post-treatment d 14, the volume of xenograft tumors was significantly reduced in the PI-88 treatment group (70.25±6.85 mm3) than in the I-88 treatment group (143.13±1718) (P<0.05). On d 15, CT value was significantly lower in the PI-88 treatment group (15.18±0.91 mm2) than in the control group (19.23±2.03 mm2) (P<0.05), and staining signals for both HPSE (28.70±6.39 vs 87.55±22.03, P<0.01) and VEGF (47.10±8.18 vs 94.40±14.47, P<0.01) in the control group than in the treat group. Conclusions: Co-injection of xenograft tumor cells with matrigel may offer a reliable and more efficient approach of establishing animal models of esophageal cancer. PI-88 may inhibit esophageal tumor growth and angiogenesis, possibly, through VEGF- and HPSE-dependent mechanisms.

河北省卫生厅重点科研项目资助（No. 20120130）。