三氧化二砷诱导人胃癌裸鼠移植瘤细胞凋亡及其对Fas/FasL表达的影响

Effect of arsenic trioxide in inducing apoptosis and expression of Fas/FasL of gastric tumor cells in nude mice

目的探讨三氧化二砷(As2O3)对Fas/FasL表达的影响及其在诱导肿瘤细胞凋亡中的作用。方法雄性BALB/C-nu/nu裸鼠30只,建立人胃癌裸鼠移植瘤模型后,随机分为3组,即对照组、As2O3低剂量组和As2O3高剂量组。As2O3低剂量组和高剂量组分别按2.5 mg/kg和5 mg/kg剂量给予As2O3腹腔注射治疗;对照组给予等体积生理盐水。测量瘤块体积观察肿瘤的生长情况;采用电镜观察和原位末端标记(TUNEL)法检测肿瘤细胞的凋亡情况;采用免疫组化法检测Fas/FasL的表达。结果As2O3治疗组瘤块的平均体积均显著小于对照组(P<0.05);As2O3治疗组肿瘤组织中凋亡细胞的数量较对照组显著增多(P<0.01);As2O3治疗组肿瘤细胞的Fas表达显著高于对照组(P<0.05),但FasL的表达两组间无显著性差异(P>0.05)。结论As2O3对人胃癌移植瘤的生长具有明显的抑制作用,其机制可能与上调Fas表达、诱导胃癌细胞凋亡有关。

Objective To study the effect of arsenic trioxide （As2O3） on the expression of Fas/FasL and in inducing apoptosis of gastric tumor cells in nude mice. Methods The xenograft model was established in 30 male BALB/C-nu/nu mice. The mice were randomly divided into 3 groups and injected intraperitoneally with As2O3 （2.5 mg/kg or 5 mg/kg） or with saline solution of the same volume respectively. Tumor growth was detected by measuring tumor volume. Apoptosis of the tumor cells was measured with transmission electron microscope （TEM） and TdT-mediated dUTP nick end labeling （TUNEL）. The expression of Fas/FasL in the tumor cells was detected with immunohistochemistry. Results Tumor volume in As2O3-treated groups was smaller than that in control group （P〈0.05）. Apoptotic cells in the As2O3-treated groups significantly outnumbered than those in control group （P〈0.01）. The expression of Fas in tumor cells was higher in the As2O3-treated groups than in control group （P〈 0.05）, but FasL expression of tumor ceils did not differ between the treated groups and control group （P〉0.05）. Conclusion As2O3 can obviously inhibit the growth of human gastric tumor. One of the mechanisms is upregulation of Fas gene that can induce the apoptosis of gastric ceils.