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背景与目的:三氧化二砷(arsenictrioxide,As2O3)已成功地应用于急性早幼粒细胞白血病的临床化疗,并已用于治疗肝癌、结肠癌、胃癌等的实验研究。本研究探讨As2O3对人卵巢癌细胞株3AO细胞裸鼠腹腔种植转移的影响及其作用机制。方法:采用四甲基偶氮唑蓝(methylthiazolyltetrazolium,MTT)法检测不同浓度As2O3作用48h对人卵巢癌细胞株3AO细胞的生长抑制率,并与顺铂(cisplatin,cDDP)进行比较。取4×106个3AO细胞接种于裸鼠腹腔,96h后随机分为5组,分别腹腔内注射生理盐水、3mg/kg顺铂及0.8、1.2、2.4mg/kgAs2O3,观察3AO细胞在各组裸鼠的成瘤率、裸鼠的死亡率及生存期;采用流式细胞术观察As2O3作用后3AO细胞中Fas、FasL、nm23基因表达的变化。结果:As2O3能明显抑制3AO细胞的生长,抑制作用呈浓度依赖性,与顺铂相比差异有显著性(P<0.05);As2O3能明显降低3AO细胞的裸鼠成瘤率及荷瘤鼠的死亡率,延长荷瘤鼠的生存期,与顺铂相比差异有显著性(P<0.05);As2O3使裸鼠腹腔种植瘤Fas基因及nm23基因的表达水平升高(P<0.05),而对FasL基因的表达无影响(P>0.05)。结论:As2O3对人卵巢癌裸鼠腹腔种植具有明显的抑制作用,其机制可能与Fas基因及nm23基因的过度表达有关。
BACKGROUND & AIM: Arsenictrioxide (As2O3) has been successfully used in the clinical chemotherapy of acute promyelocytic leukemia and has been used to treat liver cancer, colon cancer and gastric cancer. This study was to investigate the effect and mechanism of As2O3 on peritoneal metastasis of human ovarian cancer cell line 3AO. Methods: MTT method was used to detect the growth inhibition rate of human ovarian cancer cell line 3AO with different concentrations of As2O3 for 48h, and compared with cisplatin (cDDP). 4 × 106 3AO cells were inoculated into the peritoneal cavity of nude mice and then randomly divided into 5 groups after 96 hours. The rats were injected intraperitoneally with normal saline, 3mg / kg cisplatin and 0.8,1.2,2.4mg / kg As2O3, respectively. Tumorigenesis rate of mice, mortality and survival of nude mice; the expression of Fas, FasL and nm23 in 3AO cells was observed by flow cytometry. Results: As2O3 could significantly inhibit the growth of 3AO cells in a concentration-dependent manner, which was significantly different from that of cisplatin (P <0.05); As2O3 could significantly reduce the tumorigenicity of 3AO cells in nude mice and the tumor- (P <0.05). As2O3 could increase the expression of Fas and nm23 in peritoneal xenografts in nude mice (P <0.05), while the survival rate of tumor-bearing mice prolonged FasL gene expression had no effect (P> 0.05). Conclusion: As2O3 can significantly inhibit the peritoneal implantation of human ovarian cancer in nude mice. The mechanism may be related to the overexpression of Fas and nm23 genes.