目的 探讨三氧化二砷(As2O3)对小鼠结肠癌CT26细胞皮下移植瘤的影响.方法 取对数生长期CT26细胞株制成单细胞悬液接种在BALB/c小鼠前肢腋下复制皮下移植瘤模型.将荷瘤小鼠随机分为3组:对照组、低浓度组及高浓度组,每组9只,分别连续尾静脉注射等体积生理盐水、1.0 mg/(kg·d)亚砷酸氯化钠注射液、2.0 mg/(kg·d)亚砷酸氯化钠注射液10 d,末次用药后24 h处死小鼠取肿瘤组织.测量肿瘤体积和重量,计算肿瘤生长抑制率;HE染色观察肿瘤细胞的形态学特征;免疫组化检测肿瘤组织Ki-67、Survivin、Bcl-2及Caspase-3的表达;Western blot测定各组肿瘤组织中Caspase-3蛋白的表达情况.结果 (1)与对照组比较,低、高浓度组小鼠皮下移植瘤体积较小,重量较轻,肿瘤生长明显受到不同程度的抑制(P〉0.05).(2)肿瘤组织HE染色,镜下观察药物低、高浓度组中肿瘤细胞的形态和分化发生明显的变化,细胞增殖受到明显抑制,核分裂象大量减少,高浓度组中这种表现更为明显.(3)免疫组化学显示,低、高浓度组中Ki-67、Survivin及Bcl-2的阳性表达明显降低,而同时Caspase-3的阳性表达则明显增强,与对照组比较差异有统计学意义(P〉0.05).(4)Western blot结果显示,低、高浓度组中的Caspase-3蛋白表达量不同程度地升高,与对照组比较差异有统计学意义(P〉0.05).结论 As2O3可明显抑制小鼠结肠癌CT26细胞皮下移植瘤的生长,表现为能有效地抑制肿瘤细胞的增殖,促进细胞凋亡.
Objective To study the effect of arsenic trioxide ( As203 ) on subcutaneously implanted tumors of co- lon carcinoma cells (CT26) in mice. Methods CT26 cells were cultivated and inoculated into subcutaneous tissue of right armpit of mice to copy subcutaneous implanted tumor model successfully. The mice were randomly divided into three groups : saline group ( Group C), low concentration of As2O3 group [ 11.0 mg/( kg·d), Group L ], high concentration of As203 group[ 12. 0 mg/(kg ~ d), Group HI. The mice were sacrificed 24 hours after of the last treatment on the 10th day. The tumor volumes and weight were measured. Tumor growth inhibition rate was also calculated. Histopathology was performed, while immnnohistochemistry was applied for assessment of the expression of Ki -67, Survivin, Bcl -2 and Caspase - 3, and Western blot was used for assessment of the expression of Caspase - 5. Results The volume and weight of the tumors were significantly smaller and lighter in the treatment groups. Suppressed proliferation and reduced mitosis were observed in treatment groups, especially in Group H. The expression of Ki -67, Survivin and Bcl -2 was signifi- cantly lower, while the positive Caspase - 3 rates were significantly higher in the treatment groups. The expression of Caspase -3 in the treatment groups were significantly up -regulated in treatment groups. Conclusion As2 03 effectively inhibits the growth of implanted tumors of colon carcinoma via proliferation suppression and apoptosis promotion of CT26 cells.