三氧化二砷联合阿司匹林对人胃癌裸鼠移植瘤生长的影响

Effect of Arsenic Trioxide Combined with Aspirin on the Growth of Human Gastric Adenocarcinoma Graft in Nude Mice

目的研究三氧化二砷(As2O3)、阿司匹林(Asp)及二者联用对人胃腺癌SGC-7901裸鼠移植瘤生长的抑制作用。方法建立人胃腺癌SGC-7901裸鼠左腋窝外侧皮下移植瘤模型31只,随机分为4组:生理盐水对照组7只,Asp组8只,As2O3组8只,联合用药组8只;均腹腔给药,连续用药14天。停药48 h后处死裸鼠,测量各组裸鼠移植瘤体积、重量变化,计算肿瘤抑制率;观察移植瘤及各组织(心、肝、肾等)变化;采用免疫组化SP法检测增殖相关蛋白Ki 67及凋亡抑制蛋白Bcl-2的表达情况,Western blot检测凋亡相关蛋白Bax的表达情况。结果联合用药组肿瘤体积及重量明显低于对照组,差异有统计学意义(P<0.05),肿瘤重量与As2O3组、Asp组比较,差异均有统计学意义(均P<0.05);As2O3组、Asp组及联合用药组体积抑瘤率分别为59.12%、47.60%、76.70%;重量抑瘤率分别为35.60%、45.44%、63.90%。SP染色显示,与对照组比较,As2O3组、Asp组、联合用药组均可不同程度下调蛋白Ki 67和Bcl-2表达,差异均有统计学意义(P<0.05),联合用药组与As2O3组、Asp组比较,差异均有统计学意义(均P<0.05)。Western blot结果显示:联合用药组Bax的表达与其他组比较明显增高,差异均有统计学意义(P<0.05)。结论联合应用As2O3和Asp对抑制胃癌细胞生长具有一定协同增效作用,且未发现明显的不良反应。

Objective To investigate the inhibitory effect of arsenic trioxide, aspirin and their combination on the growth of human gastric adenocarcinoma SGC-7901 graft in nude mice. Methods Thirty-one model nude mice with transplanted tumor of human gastric adenocarcinoma SGC-7901 were established successfully by fixing tumor tissue under the left axillary subcutaneously. They were randomly divided into 4 groups and treated respectively with normal saline （control group, n =7）, aspirin （Asp group, n = 8）, arsenic trioxide （AT group, n = 8）, and AT ＋ Asp （ combined treated group, n = 8）, medicated by intraperitoneal injection for 14 successive days. All mice were sacrificed 48 h after the final medication, the transplanted tumor mass volume and weight were meas- ured to calculate the tumor inhibition rate, and changes of tumors and tissues of heart, liver, and kidney, etc were observed. Moreover, expressions of proliferation associated protein Ki67 and apoptosis inhibitory protein Bcl-2 were detected by immunohistochemical SP method, and expression of apoptosis associated protein Bax was detected by Western blotting. Results After terminating the medication, in the combined treated group the tumor volume and weight were significantly lower than those in the control group （ P 〈 0.05） and the tumor weight was lower than that in the AT and Asp groups （both P 〈0.05）. The volume inhibition rate was 59. 12% in the AT group, 47, 60% in the Asp group, and 76.70% in the combined treated group, and the weight inhibition rate in them 35.60%, 45.44% and 63.90%, respectively. Immunochemical staining showed that as compared with the control group, expressions of Ki67 and Bcl-2 were down-regulated in all the three treated groups to some extent （ all P 〈0.05）, and significant difference was also shown in treated group with the other two treated groups （ P 〈 0.05） comparison of the two indices between the combined The expression of Bax was higher in the combined treated group than in other groups （all P 〈 0.05）. Conclusion Combined use of AT and Asp has certain cooperative effect in inhibiting the growth of gastric carcinoma cells without obvious toxic-side effects.