三氧化二砷对人乳腺癌裸鼠移植瘤的抑制作用

Inhibitory effect of arsenic trioxide on human carcinoma of breast cells transplanted in nude mice

目的探讨三氧化二砷对人雌激素受体阴性乳腺癌细胞系MDA—MB-435s在裸鼠体内生长的影响及其作用机制。方法建立乳腺癌细胞系MDA—MB-435s的裸鼠体内移植瘤模型，将24只荷瘤裸鼠随机分成4组，即生理盐水（Ns）组、顺铂（DDP）组、低剂量三氧化二砷组（1．5mg／kg）、高剂量三氧化二砷组（3．0mg／kg）。比较各组的抑瘤作用及应用免疫组化技术分别检测PCNA、Caspase-3在各组之间表达情况。结果用药后不同剂量三氧化二砷组和顺铂组均能显著抑制人乳腺癌移植瘤在裸鼠体内的生长，移植瘤的大小和重量显著低于生理盐水组（P〈0．05）。免疫组化结果表明：生理盐水组移植瘤组织中PCNA蛋白大量表达，Caspase-3蛋白少量表达。经不同剂量三氧化二砷或顺铂处理后PCNA蛋白的表达下降，而Caspase3蛋白的表达上调，与生理盐水比较差异有统计学意义（P〈0．05）。结论三氧化二砷可以通过抑制PCNA的增殖及增加Caspase-3的凋亡作用来抑制肿瘤生长，且呈剂量依赖性。

Objective To explore the antitumor effect of arsenic trioxide on human carcinoma of breast cell strain MDA - MB -435s transplanted in nude mice. Methods To set up the model of ER negative breast cancer of nude mice with MDA - MB -435s xenografts; to randomly divided 24 female BALB/C -nu/nu nude mice with tumor into four groups：normal saline group, cisplatin group, low dose arsenic trioxide group （1.5 mg/kg）, high dose arsenic trioxide group （3.0 mg/kg）. To comparison the role of the tumor growth inhibition of each group, and to detection the expressions of PCNA and Caspase -3 induced by arsenic trioxide examined by immunohistochemical method. Resluts These treatment groups can significantly inhibit the tumor growths, and make the tumor volumes and the weights significantly less than those of the control group （ P 〈 0.05 ）. The immunohistochemical staining showed that： in control group, the expression of Caspase -3 protein positive cells decreased, and the expression of PCNA protein positive cells increased; In treatment group, the expression of Caspase -3 protein positive cells increased, and the expression of PCNA protein positive cells decreased. There are significant differences in the expressions of Caspase -3 protein and PCNA protein positive cells between treatment group and control group （ P 〈 0.05 ）. Conclusions Arsenic trioxide may inhibit the tumor growths by decreasing the expression of PCNA protein and increasing the expression of Caspase -3 protein, and in a dose - dependent manner.