培哚普利和苯那普利对食管鳞癌荷瘤裸鼠的干预研究

Study on the effect of perindopril and benazepril on nude mice bearing esophageal squamous cell carcinoma

目的探索血管紧张素I转化酶抑制剂（ACEI）在食管鳞癌细胞株中是否存在抑瘤作用。方法应用RT—PCR法在食管鳞癌细胞株KYSE30、TE-1、EC109、EC9706中筛选出血管内皮生长因子（VEGF）mRNA表达水平最高者，并将其用于接种和建立裸鼠移植瘤模型。成瘤后将裸鼠均分为对照组、培哚普利组、苯那普利组（n=6），分别予0．9％NaCl溶液、培哚普利（4mg／kg）、苯那普利（6mg／kg）干预。测定各组裸鼠移植瘤的体积，计算抑瘤率。免疫组织化学法检测裸鼠移植瘤瘤体组织内CD31的表达，并计算肿瘤微血管密度（MVD）。结果EC9706细胞株中VEGFmRNA表达水平最高。在第2和第3周时，各组移植瘤体积无明显差异。在第4和第5周时，培哚普利组移植瘤体积与对照组比较无明显差异，抑瘤率分别为24．6％和21．1％，苯那普利组和对照组比较差异均有统计学意义（t=-2．450和-3．120，P=0．035和0．008），抑瘤率分别为33．1％和45．4％。经培哚普利和苯那普利干预后裸鼠移植瘤组织内CD31表达水平有所降低。苯那普利组MVD明显低于对照组（10．98±1．18比13．98±1．76，t=-3．732，P=0．002），培哚普利组（12．41±1．15）则与对照组差异无统计学意义（t=-2．053，P=0．07）。结论苯那普利（6mg／kg）能明显抑制EC9706裸鼠移植瘤生长，抑制肿瘤新生血管形成可能是其抑瘤机制之一。培哚普利（4mg／kg）可能存在类似作用。

Objective To investigate whether there was inhibitory effect of angiotensin-I converting enzyme inhibitors （ACEI） on esophageal carcinoma cell line. Methods The highest expression of vascular endothelial growth factor （VEGF） at mRNA level was screened in esophageal squamous cell carcinoma cell lines KYSE30, TE-1, EC109 and EC9706 by reverse transcription- polymerase chain reaction （RT-PCR） and which was transplanted and established nude mice xenografts model. After tumor formed, the nude mice were evenly divided into control group, perindopril group and benazepril group （n： 6） of which 0.9 ~ saline, 4 mg/kg perindopril and 6 mg/kg benazepril was given respectively to nude mice in each group. The tumor size and the tumor inhibitory rate were measured. The expression of CD31 in xenograft tumor was tested by immunohistochemistry and the microvessel density （MVD） was assessed. Results The highest expression of VEGF at mRNA level was in EC9706 cell line. At second and third week, there was no significant difference in xenograft tumor size between each group. At fourth and fifth week, there was no significant difference in xenograft tumor size between perindopril group and control group, and the tumor inhibitory rate was 24.6 % and 21.1%. There was significant difference between benazepril group and control group （t= -2. 450 and -3. 120, P=0. 035 and 0. 008）, and the tumor inhibitory rate was 33.1% and 45.4%. After treated with perindopril and benazepril, the expression of CD31 in xenograft tumor of nude mice decreased. The MVD of benazepril group was significantly lower than that of control group （10.98± 1.18 vs 13. 98 ± 1. 76; t=- 3. 732, P= 0. 002）, and there was no significant difference between perindopril group （12. 41±1.15） and control group （t= -2. 053, P=0.07）. Conclusions Benazepril （6 mg/kg） could significantly inhibit the growth of EC9706 cell line formed xenograft tumor of nude mice. One of the possible tumor inhibitory mechanisms was inhibiting new vessel forming in tumor. Perindopril （4 mg/kg） may have the similar effect.