人脐带间充质干细胞促进肝癌细胞的增殖和转移
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国家自然科学基金(81100306),上海市科委医学引导类基金(134119a9501),南京市医学科技发展项目(201308014)


Human umbilical cord mesenchymal stem cells promote proliferation and metastasis of hepatocelluar carcinoma cells
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    摘要:

    目的:研究人脐带来源的间充质干细胞(human umbilical cord mesenchymal stem cells,UC-MSCs)在体内-体外实验中对人肝癌细胞株HepG2的增殖和转移作用-方法:将UC-MSCs在无血清DMEM/F12培养基中培养48 h,收集上清液(MSCs-CM)-加入到HepG2的培养基中,使其在HepG2培养基的终浓度为25%-50%和75%作为实验组,DMEM/F12作为对照组,采用CCK-8法检测细胞增殖效应-其后使用Transwell法检测细胞的侵袭效应-建立裸鼠皮下肿瘤模型,健康雌性裸鼠12只随机分为A(HepG2细胞单/左侧皮下成瘤)-B(UC-MSCs+HepG2预混单/左侧皮下成瘤)-C(左侧HepG2-右侧UC-MSCs+HepG2皮下成瘤)3组(n = 4),每隔7 d监测成瘤体积变化,50 d后统一处死称量肿瘤湿重-结果:经各浓度MSCs-CM 处理后HepG2细胞增殖能力较对照组明显增高(P < 0.05);实验组侵袭能力明显高于对照组(P < 0.01)-50 d后皮下肿瘤湿重测得A组(0.054 2 ± 0.011 2)g-B组(0.292 0 ± 0.156 9)g-C组[左侧(0.089 4 ± 0.024 2)g-右侧(0.332 6 ± 0.102 9)g],并且从定期体积测量数据发现,两组体积的差异随着时间的推移逐渐增大(P < 0.05)-结论:UC-MSCs能促进HepG2的生长和转移,并且这种对肿瘤的增殖和侵袭促进作用可能与UC-MSCs分泌的一些因子有关-

    Abstract:

    Objective:To investigate the effect of human umbilical cord mesenchymal stem cells on the proliferation and metastasis of human hepatocellular carcinoma cell line(HepG2)in vitro and in vivo. Methods:The UC-MSCs were cultured 48 hours in serum-free DMEM/F12 medium,and then the supernatant(MSCs-CM)was collected. The MSCs-CM was added to the culture medium of HepG2 cells to a final concentration of 25%,50% or 75%(the experimental groups). DMEM/F12 was set as control group. Cell proliferation was detected by cell counting Kit-8(CCK-8)and the migration and invasion were assessed by Transwell assays. Nude mouse subcutaneous tumor models were established. A total of 12 male nude mice were randomly divided into 3 groups(n = 4,respectively):Group A(subcutaneous injection of HepG2 on the left side),Group B(subcutaneous injection of UC-MSCs + HepG2 on the left side)and Group C(subcutaneous injection with HepG2 on the left side and UC-MSCs+HepG2 on the right side). The volume of tumor was monitored at interval of 7 days until all the mice were sacrificed for the measurements of wet tumor weights at 50th day. Results:After treatment with each concentration of MSCs-CM,the proliferation of HepG2 was significantly promoted(P < 0.05) and the invasiveness was also significantly improved(P < 0.01)compared with the control group,respectively. Significant differences of wet tumor weight and volume were observed between Group A(0.054 2 ± 0.011 2 g)and Group B(0.292 0 ± 0.156 9 g),as well as two sides of Group C(left side:0.089 4 ± 0.024 2 g;right side:0.332 6 ± 0.102 9 g,P < 0.05)mice in a time-dependent manner after 50 days. Conclusion:UC-MSCs can significantly promote proliferation and metastasis capability of HepG2 cells via increasing the release of cytokines of UC-MSCs.

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吴 宁,杭化莲,张玉玲,戴绘娟,夏 强,卞建民.人脐带间充质干细胞促进肝癌细胞的增殖和转移[J].南京医科大学学报(自然科学版),2014,(8):1003-1009

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  • 收稿日期:2014-02-19
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  • 在线发布日期: 2014-08-03
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