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医学论文范文: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
【摘要】 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2.5mg/kg和5mg/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。
【关键词】 三氧化二砷;胃癌;裸鼠;Fas/FasL;凋亡
Effect of arsenic trioxide in inducing apoptosis and expression of Fas/FasL of gastric tumor cells in nude miceWU De-dong, XIAO Yan-feng, YAO Ding-shuDepartment of Pediatrics, the Second Affiliated Hospital,Medical School of Xian Jiaotong University, Xian710004, ChinaABSTRACT: 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 (2.5mg/kg or 5mg/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 cells 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 up-regulation of Fas gene that can induce the apoptosis of gastric cells.
KEY WORDS: arsenic trioxide; gastric cancer; nude mice; Fas/FasL; apoptosis
三氧化二砷(As2O3)临床治疗急性早幼粒细胞白血病(APL)获得的显著疗效，引起人们对As2O3的高度关注和重新认识。深入研究发现，As2O3能够延长细胞周期，影响凋亡相关基因的表达。诱导肿瘤细胞分化和凋亡可能是As2O3抗肿瘤的主要机制[1-2]。细胞凋亡途径主要为两条，即线粒体途径和死亡受体途径。目前，对砷剂诱导肿瘤细胞凋亡机制的研究主要集中在线粒体途径上，而对其诱导肿瘤细胞凋亡的作用是否依赖Fas/FasL系统，报道较少。本研究以SGC7901(人淋巴结转移性胃腺癌)细胞在裸鼠皮下建立胃癌模型，用不同剂量的As2O3腹腔注射，探讨As2O3的抗癌作用及其诱导凋亡的机制医.学全.在.线www.med126.com。
1 材料与方法
1.1 主要试剂及细胞株
