三氧化二砷对裸鼠人乳腺癌移植瘤的作用及机制

目的探讨三氧化二砷（As2O3）对乳腺癌移植瘤的作用及其机制。方法建立BALB／C—nu／nu裸鼠ER阴性MDA—MB-435s人乳腺癌移植瘤模型，分别以不同浓度的As2O3、顺铂和生理盐水（NS）腹腔内注射，观察移植瘤的瘤重及抑瘤率。并用免疫组化检测乳腺癌石蜡标本中PTEN和Caspase-7的表达。结果As2O3高剂量组、As2O3低剂量组、顺铂组均能明显抑制裸鼠皮下肿瘤的生长，抑瘤率分别为48．68％、32．80％、66．67％。用药后移植瘤组织中PTEN和Caspase-7蛋白阳性细胞数显著增多（P〈0．05）。结论As2O3能明显抑制乳腺癌移植瘤的生长，其作用机制可能是通过上调PTEN和Caspase-7的表达，促进细胞的凋亡来抑制人乳腺癌细胞的生长。

Effect of arsenic trioxide and mechanism on growth of a heterologous graft model for human breast cancer in nude mice

Objective To study the inhibitory effect of arsenic trioxide （As2O3 ） on the tumor growth of breast cancer line MDA - MB - 435s implanted subcutaneously in nude mice and its mechanism. Methods BALB/C -nu/nu nude mice were subcutaneously injected with MDA -MB -435s breast cancer cells that were ER- negative, and treated with intraperitoneal injection of As2O3 and DDP indifferent concentrations. The implanted tumor was weighed, and tumor inhibition rates were calculated. The expression of PTEN and Caspase - 7 induced by As2O3 were examined by immunohistochemical method. Results The growth of implanted tumor was markedly inhibited with DDP, low dose and high dose As2O3, and the inhibitory rates were 48.68% ,32.80% ,66.67% respectively. The immunohisto- chemical staining showed that the number of PTEN and Caspase -7 protein increased markedly （ P 〈 0. 05）. Conclusions As2O3 inhabits the growth of human breast cancer cell implanted tumor. The molecular mechanism of As2O3 on induction of apoptosis of breast cancer cells may be through increasing the expression of PTEN and Caspase - 7 （ P 〈 0.05 ）.