纳米及微米磁微粒磁性顺铂微球对肝癌细胞的影响及机理
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Effects and mechanism of magnetic microsphere combination of cisplatin with micron ferric oxide particle on human hepatoma cell in vitro
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    摘要:

    目的:探讨用纳米及微米氧化铁磁核合成的磁性顺铂微球对人肝癌细胞BEL7402的影响及机理。方法:在肝癌细胞培养液中分别加入0.04~8μg/ml(按顺铂的含量计)的顺铂(CDDP)及含相应CDDP剂量的纳米磁微粒磁性顺铂微球(nCDDPmm)和微米磁微粒磁性顺铂微球(mCDDPmm),并将0μg/ml CDDP与未包裹CDDP的磁性微球作为对照,采用MTT法、细胞计数法、流式细胞仪等观察肝癌细胞的活细胞数、杀伤率、生长曲线、细胞周期、增殖指数以及凋亡。结果:(1)随药物的浓度增加,肝癌细胞的活细胞数下降,杀伤率增加,呈明显的量效关系(r值分别是0.95,0.91,0.89,P<0.01);(2)随药物的浓度增加,时间延长,肝癌细胞的生长曲线变低平,6~24h,≤0.8μg/ml时,nCDDPmm和mCDDPmm的细胞数高于CDDP(P<0.05),nCDDPmm与mCDDPmm无明显差异(P>0.05);(3)随药物的浓度增加,肝癌细胞的凋亡率增加,nCDDPmm组的凋亡率高于mCDDPmm和CDDP组(P<0.01);(4)CDDP,nCDDPmm,mCDDPmm均使肝癌细胞G0/G1期增加,S期及PI降低。结论:纳米及微米磁微粒磁性顺铂微球的抗肝癌细胞增殖作用取决于CDDP的浓度,其机理主要是诱导肝癌细胞凋亡。纳米磁微粒与微米磁微粒均有微弱促肝癌细胞增殖作用,但随作用时间延长,nCDDPmm和mCDDPmm中的CDDP从微球中缓慢释放后就足以消除磁微粒的影响。

    Abstract:

    Objective:
    To investigate the effects and mechanism of magnetic microsphere combination of cisplatin with nano or micron ferric oxide particle on human hepatoma cell(HHC). Methods : A human hepatoma cell line BEL7402 was used in this study, 0.04μg/ml~8μg/ml of cisplatin(CDDP), cisplatin nanoferric oxide magnetic microsphere(nCDDPmm) and microferric oxide magnetic microsphere(mCDDPmm) were administered to the culture solution for culturing the BEL7402 cell as the experimental groups,and in the control groups were administered with cisplatin 0μg/ml and magnetic microsphere without cisplatin respectively. The optic density of viable cell, cytotoxity index, growth curve of cell, cell cycle, proliferation index and apoptosis were assayed by MTT method, cell count and flow cytometry respectively. Results : (1)The viable cell's optic density decreased and the cytotoxity index increased in human hepatoma cell following increasing dosages of CDDP, nCDDPmm and mCDDPmm in culture solution,presenting a dosedependent manner(r value of three drugs were 0.95, 0.91 and 0.89 respective, P<0.01). (2)The growth curve of human hepatoma cell numbers developed smoothly, when the dosage of the drugs and timing increased. The cell numbers in nCDDPmm group and mCDDPmm group were higher than that in CDDP group, when dose ≤0.8μg/ml, and timing from 6h to 24h. The cell numbers was no significant difference(P>0.05)between nCDDPmm and mCDDPmm. (3)Apoptosis rate of hepatoma cell increased (P<0.01), when dose of CDDP, nCDDPmm and mCDDPmm increased. The apoptosis rate in nCDDPmm group was highter than that in mCDDPmm group (P<0.01). (4)The G0/G1 phase increased, and S phase decreased, when human hepatoma cell was treated by CDDP,nCDDPmm and mCDDPmm. Conclusions:The antineoplastic effects of nCDDPmm and mCDDPmm depend on the concentration of CDDP, the mechanism is mainly the apoptosis occurred in human hepatoma cell. Ferric oxide particles of nano and micron have faint stimulative proliferation of human hepatoma cell, however,it is enough to eliminate the influence of ferric oxide particle on hepatoma cell as the CDDP released slowly from nCDDPmm and mCDDPmm with time.

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何跃明, 吕新生,艾中立,刘志苏,王平康.纳米及微米磁微粒磁性顺铂微球对肝癌细胞的影响及机理[J].中国普通外科杂志,2004,13(3):7-184.
DOI:10.7659/j. issn.1005-6947.2004.03.007

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  • 在线发布日期: 2004-03-25