三氧化二砷对A549肺癌移植瘤生长及Ki-67表达的影响

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目的探索三氧化二砷(As2O3)对肺癌移植瘤生长、肿瘤组织结构及Ki-67表达的影响。方法构建A549肺癌裸鼠皮下移植瘤模型,随机分为空白对照(生理盐水)组、As2O32.5 mg·kg-1组、As2O35.0 mg·kg-1组、VP-16(20 mg·kg-1)组和索拉非尼(30 mg·kg-1)组,每组5只,每日给药1次,连续21 d。比较各组移植瘤体积、计算肿瘤生长抑制率,HE染色观察肿瘤显微结构,免疫组化方法观察肿瘤组织Ki-67表达情况。结果给药结束后,四个药物处理组的肿瘤平均体积均小于空白对照组(P<0.01),索拉非尼组的肿瘤生长抑制率(64.2%)最高,As2O35.0 mg·kg-1组、VP-16组和As2O32.5 mg·kg-1组的抑制率分别为48.1%、44.4%和31.1%;镜下可见As2O3处理组的肿瘤间质较空白对照组增加,并有腺腔形成;As2O3和VP-16可以降低Ki-67水平(P<0.01),而索拉非尼组的Ki-67水平与空白对照组无显著差别(P>0.05)。结论 As2O3能抑制A549肺癌移植瘤的生长,诱导肿瘤组织腺样分化,减低肿瘤组织Ki-67水平。 Objective To investigate the effects of As2O3 on the growth, tumor structure and Ki-67 expression in lung cancer xenografts. Methods A subcutaneous xenograft model of A549 lung cancer in nude mice was established and randomly divided into blank control group (saline group), As2O32.5 mg.kg-1 group, As2O35.0 mg.kg-1 group and VP-16 (20 mg.kg- -1) group and sorafenib (30 mg · kg -1) group, 5 rats in each group. The rats were given once daily for 21 days. The volume of tumor in each group was compared, the growth inhibition rate was calculated, the microstructure of tumor was observed by HE staining, and the expression of Ki-67 in tumor tissue was observed by immunohistochemistry. Results After the treatment, the average volume of tumors in the four drug-treated groups was less than that in the blank control group (P <0.01), the tumor growth inhibition rate (64.2%) in the sorafenib group was the highest, the As2O3 was 35.0 mg · kg-1 The inhibitory rates of group VP-16 and group As2O32.5 mg · kg-1 were 48.1%, 44.4% and 31.1%, respectively. Compared with the blank control group, As2O3 and VP-16 can reduce the Ki-67 level (P <0.01), but there was no significant difference between the sorafenib group and the blank control group (P> 0.05). Conclusion As2O3 can inhibit the growth of A549 lung cancer xenografts, induce adenoid differentiation of tumor tissues and decrease the Ki-67 level in tumor tissues.
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