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醫(yī)學(xué)論文范文:三氧化二砷誘導(dǎo)人胃癌裸鼠移植瘤細(xì)胞凋亡及其對(duì)Fas/FasL表達(dá)的影響
【摘要】 目的 探討三氧化二砷(As2O3)對(duì)Fas/FasL表達(dá)的影響及其在誘導(dǎo)腫瘤細(xì)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，隨機(jī)分為3組，即對(duì)照組、As2O3低劑量組和As2O3高劑量組。As2O3低劑量組和高劑量組分別按2.5mg/kg和5mg/kg劑量給予As2O3腹腔注射治療;對(duì)照組給予等體積生理鹽水。測量瘤塊體積觀察腫瘤的生長情況;采用電鏡觀察和原位末端標(biāo)記(TUNEL)法檢測腫瘤細(xì)胞的凋亡情況;采用免疫組化法檢測Fas/FasL的表達(dá)。結(jié)果 As2O3治療組瘤塊的平均體積均顯著小于對(duì)照組(P<0.05);As2O3治療組腫瘤組織中凋亡細(xì)胞的數(shù)量較對(duì)照組顯著增多(P<0.01);As2O3治療組腫瘤細(xì)胞的Fas表達(dá)顯著高于對(duì)照組(P<0.05)，但FasL的表達(dá)兩組間無顯著性差異(P>0.05)。結(jié)論 As2O3對(duì)人胃癌移植瘤的生長具有明顯的抑制作用，其機(jī)制可能與上調(diào)Fas表達(dá)、誘導(dǎo)胃癌細(xì)胞凋亡有關(guān)。
【關(guān)鍵詞】 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)臨床治療急性早幼粒細(xì)胞白血病(APL)獲得的顯著療效，引起人們對(duì)As2O3的高度關(guān)注和重新認(rèn)識(shí)。深入研究發(fā)現(xiàn)，As2O3能夠延長細(xì)胞周期，影響凋亡相關(guān)基因的表達(dá)。誘導(dǎo)腫瘤細(xì)胞分化和凋亡可能是As2O3抗腫瘤的主要機(jī)制[1-2]。細(xì)胞凋亡途徑主要為兩條，即線粒體途徑和死亡受體途徑。目前，對(duì)砷劑誘導(dǎo)腫瘤細(xì)胞凋亡機(jī)制的研究主要集中在線粒體途徑上，而對(duì)其誘導(dǎo)腫瘤細(xì)胞凋亡的作用是否依賴Fas/FasL系統(tǒng)，報(bào)道較少。本研究以SGC7901(人淋巴結(jié)轉(zhuǎn)移性胃腺癌)細(xì)胞在裸鼠皮下建立胃癌模型，用不同劑量的As2O3腹腔注射，探討As2O3的抗癌作用及其誘導(dǎo)凋亡的機(jī)制醫(yī).學(xué)全.在.線gydjdsj.org.cn。
1 材料與方法
1.1 主要試劑及細(xì)胞株
