氧化砷抑制结肠癌裸鼠皮下移植瘤生长及作用机制的研究

Arsenic trioxide inhibits the growth of human colon cancer cell subcutaneous implanted tumor and its mechanism

目的 研究氧化砷 (As2 O3 )对人结肠癌SW4 80细胞裸鼠皮下移植瘤生长的抑制作用及其作用机制。方法 建立BALB/C nu/nu裸鼠SW4 80结肠癌皮下移植瘤模型 ,以不同浓度As2 O3 行腹腔内注射治疗 ,与 5 氟脲嘧啶 (5 FU)治疗进行对比 ,观察移植瘤的瘤重及瘤重抑制率 ,TUNEL法检测移植瘤SW4 80细胞凋亡率 ,免疫组织化学法检测bcl 2 ,Fas基因表达水平的变化。结果 5 FU、低剂量As2 O3 及高剂量As2 O3 均能明显抑制裸鼠皮下肿瘤的生长 ,抑瘤率分别为 4 1.5 1%、5 3.2 1%和 5 8.0 2 % ,As2 O3 对移植瘤的生长抑制作用明显强于 5 FU ,两者比较有显著性差异 (P <0 .0 1)。两种浓度As2 O3 组SW4 80细胞凋亡率明显高于 5 FU。移植瘤组织中bcl 2蛋白阳性细胞数明显减少 ,Fas蛋白阳性细胞数明显增加。结论 As2 O3 对结肠癌移植瘤的生长具有明显的抑制作用 ,可诱导移植瘤SW4 80细胞凋亡 ,其作用的分子机制可能是下调bcl 2基因表达 ,上调Fas基因表达。

Objective To study the inhibitory effect of arsenic trioxide(As 2O 3) on the growth of SW480 cell subcutaneous implanted tumor in nude mice and its mechanism.Methods BALB/C-nu/nu nude mice were subcutaneously injected with SW480 colon cancer cell line,and treated with intraperitoneal injection of As 2O 3 and 5-FU in different concentrations.The implanted tumor was weighed,and the tumor inhibition rates were calculated .The apoptosis rates of SW480 cells were assessed by TUNEL method. The expressions of bcl-2 and Fas induced by As 2O 3 were examined by immunohistochemistry.Results The tumor-bearing mice were treated with 5-FU, low dose and high dose As 2O 3 .The growth of implanted tumor was markedly inhibited ,the inhibitory rates being 41.51% ,53.21% and 58.02%,separately.The inhibitory effect of As 2O 3 was significantly stronger than that of 5-FU(P<0.01).The apoptosis rates of SW480 induced by As 2O 3 were significantly higher than those of 5-FU (P<0.01) .The immunohistochemical staining showed that the number of bcl-2 protein positive cells decreased and the number of Fas protein positive cells increased.Conclusion As 2O 3 inhibits the growth of human colon cancer cell implanted tumor and induces apoptosis of SW480.The molecular mechanism of As 2O 3 on induction of apoptosis of colon cancer cells may be decrease of the expressions of bcl-2 and increase of the expressions of Fas.