氧化砷抗胰腺癌作用及其机制的实验研究

Anti-tumor Effect and Mechanism of Action of Arsenic Oxide on Pancreatic Carcinoma: An Experimental Study

目的:探讨氧化砷(As_2O_3)体外体内抗胰腺癌作用及其可能机制。方法:应用MTT比色法、流式细胞仪、裸鼠肾包膜下移植瘤抑制试验和细胞形态学方法进行检测。结果:As_2O_3抑制胰腺癌细胞生长并具有时间与浓度依赖性,6天组抑制50％细胞生长的药物浓度(IC_(50))为0.625～1.25μg/ml。癌细胞在As_2O_3作用下,G0/G1期细胞比例、凋亡指数(AI)增高,增殖指数(PI)下降,AI/PI比例增大。As_2O_3能显著抑制肾包膜下胰腺癌移植瘤生长。电镜检查证实As_2O_3诱导的胰腺癌细胞具有凋亡与分化特征。结论:As_2O_3抗胰腺癌细胞作用主要通过诱导细胞凋亡与分化而得到体现。

Background/Aims: To investigate the anti-tumor effect of Arsenic oxide (As2O3) and its mechanism of action in pancreatic carcinoma. Methods: MTT colorimetric assays, flow cytometry, the subrenal capsule (SRC) xenograft assay in nude mice and cell morphologic study were performed. Results: Inhibitory effect on pancreatic carcinoma cell growth was observed and was time and concentration dependently. The 50% inhibitory concentration (IC50) on cell growth in 6 days' group was 0.625-1.25ug/ml. As2O3 increased the percentage of cell population in G0/G1 phase and cell apoptosis index (AI), but reduced the proliferation index (PI). AI/PI was higher in As2O3 treated groups than that of control. As2O3 inhibited significantely the growth of SRC pancreatic carcinoma xenografts. The morphologic features were primarily apoptosis and differentiation. Conclusions: Induction of cell apoptosis and differentiation might be the important mechanism of action of Arsenic oxide in pancreatic carcinoma.