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题名: Development of an in vitro multicellular tumor spheroid model using microencapsulation and its application in anticancer drug screening and testing
作者: Zhang, XL;  Wang, W;  Yu, WT;  Xie, YB;  Zhang, XH;  Zhang, Y;  Ma, XJ
通讯作者: 马小军
刊名: BIOTECHNOLOGY PROGRESS
发表日期: 2005-07-01
DOI: 10.1021/bp050003l
卷: 21, 期:4, 页:1289-1296
收录类别: SCI
文章类型: Article
部门归属: 18
项目归属: 1802
产权排名: 1;1
WOS标题词: Science & Technology ;  Life Sciences & Biomedicine
类目[WOS]: Biotechnology & Applied Microbiology ;  Food Science & Technology
研究领域[WOS]: Biotechnology & Applied Microbiology ;  Food Science & Technology
英文摘要: In this study, an in vitro multicellular tumor spheroid model was developed using microencapsulation, and the feasibility of using the microencapsulated. multicellular tumor spheroid (MMTS) to test the effect of chemotherapeutic drugs was investigated. Human MCF-7 breast cancer cells were encapsulated in alginate-poly-L-lysine-alginate (APA) microcapsules, and a single multicellular spheroid 150 mu m in diameter was formed in the microcapsule after 5 days of cultivation. The cell morphology, proliferation, and viability of the MMTS were characterized using phase contrast microscopy, BrdU-Iabeling, MTT stain, calcein AM/ED-2 stain, and H&E stain. It demonstrated that the MMTS was viable and that the proliferating cells were mainly localized to the periphery of the cell spheroid and the apoptotic cells were in the core. The MCF-7 MMTS was treated with mitomycin C (MC) at a concentration of 0.1, 1, or 10 times that of peak plasma concentration (ppc) for up to 72 h. The cytotoxicity was demonstrated. clearly by the reduction in cell spheroid size and the decrease in cell viability. The MMTS was further used to screen the anticancer effect of chemotherapeutic drugs, treated with MC, adriamycin (ADM) and 5-fluorouracil (5-FU) at concentrations of 0.1, 1, and 10 ppc for 24, 48, and 72 h. MCF-7 monolayer culture was used as control. Similar to monolayer culture, the cell viability of MMTS was reduced after treatment with anticancer drugs. However, the inhibition rate of cell viability in MMTS was much lower than that in monolayer culture. The MMTS was more resistant to anticancer drugs than monolayer culture. The inhibition rates of cell viability were 68.1%, 45.1%, and 46.8% in MMTS and 95.1%, 86.8%, and 91.6% in monolayer culture treated with MC, ADM, and 5-FU at 10 ppc for 72 h, respectively. MC showed the strongest cytotoxicity in both MMTS and monolayer, followed by 5-FU and ADM. It demonstrated that the MMTS has the potential to be a rapid and valid in vitro model to screen chemotherapeutic drugs with a feature to mimic in vivo three-dimensional (3-D) cell growth pattern.
关键词[WOS]: SOLID TUMORS ;  CELL-LINES ;  CHEMOTHERAPY ;  TISSUE ;  ASSAY ;  RESISTANCE ;  CULTURE ;  INVITRO ;  GROWTH ;  MICROCAPSULES
语种: 英语
原文出处: 查看原文
WOS记录号: WOS:000231126800036
Citation statistics: 
内容类型: 期刊论文
URI标识: http://cas-ir.dicp.ac.cn/handle/321008/92431
Appears in Collections:中国科学院大连化学物理研究所_期刊论文

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作者单位: 1.Chinese Acad Sci, Dalian Inst Chem Phys, Lab Biomed Mat Engn, Dalian 116023, Peoples R China
2.Chinese Acad Sci, Grad Sch, Beijing 100039, Peoples R China

Recommended Citation:
Zhang, XL,Wang, W,Yu, WT,et al. Development of an in vitro multicellular tumor spheroid model using microencapsulation and its application in anticancer drug screening and testing[J]. BIOTECHNOLOGY PROGRESS,2005,21(4):1289-1296.
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