【作者】 李利； 苏杏满； 程建新； 吴小华；

【Author】 Li Li Su Xing-Man Cheng Jian-Xin Wu Xiao-Hua Department of Obsterics and Gynecology , the fourth hospital of Hebei medical university & Hebei provincial tumor hospital, Shijiazhuang, 050011, China

【机构】 河北医科大学第四医院暨河北省肿瘤医院妇产科；

【摘要】 目的:子宫内膜癌是妇科最常见的肿瘤,居妇女全身肿瘤的第四位。进展期及复发性子宫内膜癌的预后非常差, 平均生存率低于一年。尽管人们做了不懈的努力,治疗反应率有所提高,但生存率仍很低,而且现存的药物毒副作用较大。三氧化二砷(ATO)最初被用作一种毒素,现发现它可用于治疗食管癌,淋巴肿瘤,白血病等,且应用于前列腺癌, 膀胱癌,官颈癌的临床实验正在进行中,毒副作用轻,通过降量或控制症状可缓解,但无其对子宫内膜癌作用的报道。本研究将探讨三氧化二砷对人类子宫内膜癌细胞HEC—J—A 的作用。方法:应用四氮唑盐代谢法(MTT),流式细胞分析, 和DNA电泳分别检测三氧化二砷对HEC-1-A细胞增殖,细胞周期及细胞凋亡的影响,并和子宫内膜癌治疗药物的作用进行了比较。结果:MTT法检测了不同药物对HEC-1-A细胞增殖的影响,黄体酮(1-20μM)对HEC-1-A细胞生长无影响。安宫黄体酮在1-5 μM明显抑制细胞生长,但在较高浓度无作用。三氧化二砷,顺铂(CDDP)在1-20?M明显抑制了细胞生长,而且ATO的作用强于CDDP。进一步研究,流式细胞分析发现5 μ M ATO引起了细胞凋亡,S期和G2／M期细胞阻滞,DNA电泳发现在5-10 μ MATO作用下出现典型的梯状DNA条带。结论: 三氧化二砷明显抑制HEC-1-A细胞生长,甚至强于顺铂,机制在于引起细胞凋亡和G2／M期细胞阻滞,具有治疗子宫内膜癌的潜在应用价值。更多还原

【Abstract】 Objective: Endometrial cancer is the most common gynecologic malignancy and the fourth most common cancer in women. The prognosis for patients with more advanced or recurrent endometrial disease is poor, with a median survival of less than 1 year. Though there has been considerable progress in the treatment of advanced or recurrent gynecologic malignancy over the past decade, yet despite improving response rates, survival remains poor. In addition, cytotoxic therapy is associated with frequent severe toxicity. ATO, is known to be a toxin. Encouraging results have been observed in the treatment of esophageal carcinoma, malignant lymphoma, and leukemia. The toxic effects are mild and respond to symptomatic treatment or resolve with dose reduction. The trials in patients with advanced hormone-refractory prostate cancer, bladder or cervical cancer were under way. However, there is no report about ATO on endometrial carcinoma. At present, the study is to explore the effect of arsenic trioxide (ATO) on endometrial carcinoma HEC-1-A cells. Methods: Tet-razolium salt assay (MTT), flow cytometry and DNA fragmentation were used to measure the effect of ATO on HEC-l-A cell proliferation, cell cycle phase distribution and apoptosis, respectively. Results: Progesterone (1-20 μ M) had no effect on HEC-1-A cell proliferation ATO (5 μ M) treatment resulted in an accumulation of apoptosis, S and G2/M cell populations. MPA at concentration of 1-5 μ M significantly inhibited the cell growth, but no effect was observed at higher concentrations. ATO, CDDP significantly inhibited the cell growth at concentration of 1-20 μ M. It seems that ATO> CDDP. ATO (5 μ M) treatment resulted in an accumulation of apoptosis, S and G2/ M cell populations. DNA fragmentation assay confirmed that ATO (5-10 μ M) induced apoptosis in HEC-1-A cells. Conclusion: ATO significantly inhibited the HEC-1-A cell growth, even stronger than CDDP due to induce apoptosis and G2/M cell cycle arrest. ATO has the potential to treat endometrial carcinoma.更多还原