四硫化四砷对裸鼠卵巢癌皮下移植瘤生长的影响

Effects of tetra-arsenic tetra-sulfide on human ovarian carcinoma subcutaneously transplanted in nude mice

目的利用BALB/C裸鼠和人卵巢癌细胞株SKOV3建立裸鼠皮下移植瘤,探讨四硫化四砷在卵巢癌组织中的抑瘤作用及机制。方法建立卵巢癌SKOV3裸鼠皮下移植瘤模型,按照给药剂量(50mg/kg和100mg/kg)及肿瘤生成大小(3mm×3mm和10mm×10mm)将裸鼠随机分成小剂量早期治疗组、大剂量早期治疗组、小剂量治疗组和大剂量治疗组,分别予四硫化四砷隔日灌胃,并设裸鼠生理盐水对照组。观察四硫化四砷对肿瘤的生长的影响;RT-PCR法及Western blotting法检测四硫化四砷对肿瘤组织中Bcl-2/Bax蛋白和mRNA表达的影响。结果各组裸鼠一般情况良好。小剂量早期治疗组、大剂量早期治疗组和大剂量治疗组的抑瘤率分别为84.98%、87.55%和74.25%,与小剂量治疗组的35.19%相比,差异均有统计学意义(P<0.05)。RT-PCR显示肿瘤组织Bcl-2 mRNA表达下调和Bax mRNA表达上调,Western blotting显示其Bcl-2蛋白表达降低和Bax蛋白表达增加。结论四硫化四砷可以抑制卵巢癌裸鼠皮下移植瘤的生长,并诱导卵巢癌细胞凋亡。其作用机制可能与凋亡调控基因Bcl-2/Bax表达的改变有关。

Objective To establish the subcutaneously transplantated tumor of SKOV3 by BALB/C nude mice,evaluate the inhibitory effect of tetra-arsenic tetra-sulfide（As4S4）on the growth and apoptosis of tumor tissue,and study the anti-cancer mechanism of As4S4.Methods The BALB/C nude mice were subcutaneously implanted with SKOV3,and according to dose of medication（50mg/kg and 100mg/kg）and tumor size（3mm×3mm and 10mm×10mm） were randomly divided into small dose early group,large dose early group,small dose group and large dose group with gastric perfusion of As4S4 at different dose.The control group of normal saline was established by the same method.By the methods of RT-PCR and Western blotting,we evaluated the influence of As4S4 on the expression of Bcl-2/Bax mRNA and protein of tumor tissue.Results After being treated with different concentration of As4S4,nude mice were in good condition.Tumor-suppressing rates in small dose early group,large dose early group and large dose group were 84.98%,87.55% and 74.25%,compared with 35.19% in small dose group with significant differences（P0.05）.RT-PCR showed that the expression of Bcl-2 mRNA was down-regulated while the expression of Bax mRNA was up-regulated.Western blotting showed that the expression of Bcl-2 protein decreased while the expression of Bax protein was increased.Conclusion As4S4 could suppress the growth of implanted tumor in nude mice,and induce tumor cells apoptosis.Anti-tumor activities of As4S4may be related to the apoptosis induction and Bcl-2/Bax expression change.