As2O3对人卵巢癌裸鼠皮下移植瘤抑制作用及机制

目的探讨不同剂量的三氧化二砷（As2O3）对人卵巢癌细胞株SKOV3细胞裸鼠皮下移植瘤生长的抑制作用及其机制。方法将4×10^6个SKOV3细胞接种于裸鼠皮下，建立人卵巢癌裸鼠皮下移植瘤模型，随机分为As2O3高、中、低剂量组及生理盐水组（空白对照）、卡铂（CBP）组（阳性对照），连续给药10d，停药后24h处死裸鼠，计算移植瘤的瘤质量、抑瘤率及caspase-3基因表达水平的变化，并检测用药后裸鼠的肝、肾功能及血常规。结果As2O3对移植瘤生长的抑制作用具有剂量依赖性，各剂量As2O3组及CBP组瘤质量与生理盐水组比较均有统计学意义（F=17．931，P〈0．05）；As2O3作用后caspase-3基因的表达较空白对照组升高，差异有统计学意义（F=31．821，q=2．89～3．84，P〈0．05）。同时，As2O3各组与CBP组相比，未表现出明显的肝、肾及血液学毒性。结论As2O3对人卵巢癌移植瘤的生长具有明显的抑制作用，其机制可能与上调caspase-3基因的表达及诱导细胞凋亡有关。

ANALYSIS OF ANTI-TUMOR MECHANISM OF ARSENIC TRIOXIDE ON THE SUBCUTANEOUSLY TRANSPLANTED TUMOR OF HUMAN OVARIAN CARCINOMA IN NUDE MICE

Objective To explore the inhibitory action of arsenic trioxide （As2O3） on the growth of SKOV3 cell subcutaneously implanted tumor in nude mice. Methods Nude mice received implanted SKOV3 cells （4）〈 106） were then treated with intraperitoneal injection of different concentration of As2O3, or CBP, as controls, for 10 days. The weight of implanted tumors and the tumor inhibition rate were observed to evaluate the anti-tumor effect of As2O3. The gene expression of caspase-3 was detected by real-time RT-PCR. Results As2O3 and CBP, compared with saline, significantly inhibited the growth of transplanted tumor （P〈0. 05）, and furthermore, the inhibitory effect of As2O3 was dose-dependent. The expression of caspase-3 was significantly upregulated in the As2O3 group in contrast to the saline group （P〈0. 05）. As2O3 showed less haematologieal toxicity and no hepatic and nephritic toxicity compared with CBP. Conclusion As2 O3 can inhibit the growth of implanted human ovarian carcinoma, the mechanism may be related to the up-regulation of the activity of easpase-3 and the cell apoptosis in vivo.