三氧化二砷抑制子宫内膜癌生长的体内外实验研究  

Study on the inhibitory effects of arsenic trioxide on the growth of endometrial cancer cells in vitro and in vivo

作　　者：胡美丽[1] 李利[1] 王晓玲[2] 顾国琴[3] 齐润辉[1] 康山 

机构地区：[1]河北医科大学第四医院妇产科,石家庄050011 [2]河北医科大学第四医院病理科,石家庄050011 [3]河北医科大学第四医院检验科,石家庄050011

出　　处：《肿瘤》2009年第7期616-619,共4页Tumor

基　　金：河北省科技攻关计划资助项目(编号:04276197)

摘　　要：目的：探讨三氧化二砷（arsenic trioxide，ATO）对人子宫内膜癌HEC-1-A细胞生长的抑制作用。方法：采用MTT法比较ATO、孕酮、安宫黄体酮（medroxyprogesterone acetate，MPA）和顺铂（cisplatin，CDDP）对HEC-1-A细胞的抑制作用，应用FCM和DNA电泳检测ATO对细胞周期和细胞凋亡的影响。建立裸鼠人子宫内膜癌移植瘤动物模型，随机分为ATO低（4mg·kg^-1·d^-1）、中（6mg·kg^-1·d^-1）、高（8mg·kg^-1·d^-1）剂量组、阳性对照CDDP组（3mg·kg^-1·d^-1）及阴性对照组，腹腔连续给药14d，计算肿瘤体积和肿瘤质量抑制率。结果：1-20μmol／L ATO和CDDP可明显抑制细胞生长，且ATO对细胞的抑制作用强于CDDP。5μmol／L ATO作用后可导致细胞凋亡，并使细胞周期阻滞于S和G2／M期。低、中、高剂量ATO组和CDDP组的肿瘤体积抑制率分别为50.97％、75.58％、56.92％和52.23％，肿瘤质量抑制率分别为10.15％、29.33％、16.67％和14.69％，与阴性对照组相比差异有统计学意义（P〈0.05）。结论：ATO可抑制HEC-1-A细胞及鼠荷入子宫内膜癌移植瘤的生长，有望成为治疗子宫内膜癌的新型药物。Objective ：To explore the inhibitoR effect of arsenic troixide （ATO） on the growth of human endometrial cancer HEC-1-A ceils in vitro and in vivo. Methods：Tetrazolium salt assay （MTT） was used to compare the inhibitory effect of ATO on HEC-1-A cells with that of progesterone, medroxyprogesterone acetate （MPA） and cisplatin （CDDP）. Flow cytometry and DNA electropho- resis were used to determine the effects of ATO on cell cycle and apoptosis. Human endometrial cancer xenografted model was estab-lished in nude mice. The tumor-bearing nude mice were randomly divided into the experimental groups： ATO low dose group （4mg·kg^-1·d^-1）, medium dose group （6mg·kg^-1·d^-1）, high dose group （8mg·kg^-1·d^-1）, CDDP positive control group （3mg·kg^-1·d^-1） and saline negative control group. The drugs were administered intraperitoneally for 14 consecutive days, and then the tumor volume and tumor inhibition rate were calculated. Results： ATO 1-20μmol/L and CDDP markedly inhibited the cell growth. The inhibitory effect of ATO was higher than that of CDDP. ATO 5μmol/L treatment induced apoptosis and arrested cells at S and G2/M phase. ATO4, 6, and 8mg·kg^-1·d^-1 and CDDP 3mg·kg^-1·d^-1 inhibited tumor volume by 50.97%, 75.58% , 56.92%, and 52.23% , respectively; and inhibited the tumor weight by 10.15% , 29.33% , 16.67%, and 14.69%, respectively. The difference was significant compared with negative control group （P〈0.05）. Conclusion： ATO inhibited the growth of endometrial cancer cells HEC-1-A in vitro and in vivo. It may become a novel therapeutic reagent for the treatment of endometrial cancer.

关 键 词：子宫内膜肿瘤 药物疗法 小鼠 裸 三氧化二砷 细胞 HEC-1-A 

分 类 号：R737.33[医药卫生—肿瘤]