摘要
目的环境内分泌干扰物对人类健康的影响已引起全球的关注。本研究旨在观察双酚A（BPA）对神经母细胞瘤生长的影响及其可能机制。方法常规培养SK-N—SH细胞，接种于双侧卵巢切除（OVX）的裸小鼠皮下。可触摸到肿瘤结节时，将裸鼠随机分为3组：①对照组（OVX＋溶剂，OVX，n=9）；②E2组（OVX＋E2，500ug·kg^-1·d^-1，n=11）；③BPA组（OVX＋BPA，200mg·kg^-1·d^-1，BPAgroup，n=10）。每周2次检测皮下移植瘤体积（TV）和裸鼠体重。第18d，解剖处死所有裸鼠，称移植瘤重量。免疫组化方法检测肿瘤组织微血管内皮细胞的表达情况，在光学显微镜高倍视野下分别计数肿瘤组织的微血管密度（MVD））。用Western Blot方法检测肿瘤组织血管内皮细胞生长因子（VEGF）蛋白的表达情况。结果实验终点时，OVX组、E2组和BPA组的TV分别为（2．62±0．54）cm^3、（5．07±0．93）cm^3和（4．19±0．68）cm^3，BPA组较OVX组增高59％（P〈0．05）。3组裸鼠体重没有明显差异（P〉0．05）。3组瘤重分别为（1．64±0．18）g、（2．58±0．19）g、（2．96±0．27）g，BPA组较OVX组增高82％（P〈0．05）；3组中Ⅷ因子相关抗原均染色，E2组（22．73±1．46）及BPA组（27．76±2．24）MVD较对照组（15．14±1．12）明显增高（P〈0．01），VEGF的蛋白表达亦较对照组增高（P〈0．05）。结论BPA可促进人神经母细胞瘤裸鼠皮下移植瘤生长，微血管形成可能参与了促生长作用。
Objective To investigate the effect of bisphenol A （BPA） on human neuroblastoma SK-N-SH cells xenograft growth in nude mice. Methods SK-N-SH cells were injected subcutaneously into ovariectomized （OVX） nude mice. When the tumors were palpable, the mice were divided into three groups based on different treatment： group 1, control group （ OVX ＋ vehicle, OVX, n = 9） ; group 2, E2 group （OVX ＋ E2, 500 ug· kg^- 1· d^- 1, n = 11 ） ; group 3, BPA group （OVX ＋ BPA, 200 mg·kg^-·d^-1, n = 10）. The tumor volume （TV） and the weight of the nude mice were examined twice a week. On the 18th day, the weight of tumor tissues was measured. Microvascular endothelial cells of tumor tissues were examined by immunohistochemistry. Microvessel density （MVD） of tumor tissues was observed under high view of microscope. The protein expression of vascular endothelial growth factor （VEGF） was determined by Western Blot. Results At the end of the treatment, the TV was （2.62 ± 0. 54）cm^3 of OVX, （5. 07 ± 0. 93）cm^3 of E2, and （4. 19 ± 0. 68）cm^3 of BPA. TV was increased by 59% for the BPA group, when compared with that of OVX group （P〈0. 05）. There was no significant difference of weight between the three groups （P〉0.05）. On the 18th day, tumor weight was （1.64±0. 18） g for OVX group, （2. 58±0. 19） g for the E2 group, and （2. 96± 0. 27） g for the BPA group. Tumor weight was enhanced by 82% in the BPA group （P〈0. 05）. MVD was （22. 73 ± 1.46） for the E2 group, and （27. 76 ± 2. 24） for the BPA group. There was a significant increase comparing the OVX group （15. 14 ± 1.12, P〈0. 01）. The expression of VEGF of E2, and BPA groups was obviously increased （P〈0. 05）. Conclusions BPA could promote the growth and angiogenesis of the human neuroblastoma transplanted subcutaneously in nude mice.
出处
《中华小儿外科杂志》
CSCD
北大核心
2007年第2期64-68,共5页
Chinese Journal of Pediatric Surgery
基金
本课题由复旦大学211重点工程基金资助
