Cytotoxic effect of zinc-citrate compound on choriocarcinoma cell lines
Cytotoxic effect of zinc-citrate compound on choriocarcinoma cell lines
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DOI：
10.1016/j.placenta.2006.01.003
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发表时间：
2007-01-01
期刊：
影响因子：
3.8
通讯作者：
Park, L. -O.
中科院分区：
文献类型：
--
作者：
Bae, S. N.;Kim, J.;Park, L. -O.
本研究探讨了柠檬酸锌复合物（CIZAR）对绒毛膜癌细胞的细胞毒作用。将原代培养的正常滋养细胞（NPT）、人致瘤性低分化滋养细胞（HT）和绒毛膜癌细胞（BeWo）分别暴露于不同浓度的CIZAR (R)中并在不同时间进行培养。CCK-8法测定细胞活力。流式细胞术检测其对细胞周期进程、细胞群分布及凋亡发生率的影响。DNA阶梯和DAPI染色证实细胞凋亡的出现。端粒酶定量分析采用TRAPeze (R)端粒酶检测试剂盒。采用Western blot和caspase-3活性比色法检测CIZAR (R)诱导细胞凋亡的分子机制。在体外条件下，CIZAR (R)对绒毛膜癌细胞具有选择性细胞毒作用，并呈剂量依赖性和时间依赖性。流式细胞分析、DNA阶梯和DAPI染色表明，CIZAR (R)仅诱导BeWo细胞凋亡。仅在BeWo细胞中观察到端粒缩短。结果还显示，CIZAR (R)诱导的细胞凋亡涉及p21（WAF1）和Bax蛋白的上调和Bcl-2的下调，并伴有caspase-3的激活。综上所述，我们的研究结果表明CIZAR (R)是恶性滋养细胞（BeWo）的凋亡诱导剂。(c) 2006 Elsevier Ltd.版权所有。
This study investigated the cytotoxic effect of zinc-citrate compound (CIZAR (R)) on choriocarcinoma cell lines. Primary cultured normal trophoblast cells (NPT), human tumorigenic poorly differentiated trophoblast cell line (HT), and choriocarcinoma cell line (BeWo) were exposed to different concentrations of CIZAR (R) and cultured at different times. Cell viability was determined by CCK-8 assay. The effects on cell cycle progression, population distribution and apoptotic incidence were determined by flow cytometry. The appearance of apoptosis was confirmed by DNA laddering and DAPI staining. The quantitative analysis of telomerase was measured by TRAPeze (R) telomerase detection kit. The molecular mechanism of CIZAR (R)-induced apoptosis was examined with Western blot analysis and colorimetric caspase-3 activity assay. In in vitro condition, CIZAR (R) had a selective cytotoxic effect on choriocarcinoma cell line in dose- and time-dependent patterns. Flow cytometric analysis, DNA laddering, and DAPI staining indicated that BeWo cells only have been induced apoptosis by CIZAR (R). Shortening of telomere was also observed only in BeWo cells. Results also displayed that CIZAR (R)-induced apoptosis involves the up-regulation of p21(WAF1) and Bax protein and down-regulation of Bcl-2 which were accompanied by the activation of caspase-3. Taken together, our results suggest that CIZAR (R) is an apoptotic inducer in malignant trophoblast cells (BeWo). (c) 2006 Elsevier Ltd. All rights reserved.