Development of an in Vitro Multicellular Tumor Spheroid Model Using Microencapsulation and Its Application in Anticancer Drug Screening and Testing
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- 作者：Xulang Zhang ; Wei Wang ; Weiting Yu ; Yubing Xie ; Xiaohui Zhang ; Ying Zhang ; and Xiaojun Ma
- 刊名：Biotechnology Progress
- 出版年：2005
- 出版时间：August 2005
- 年：2005
- 卷：21
- 期：4
- 页码：1289 - 1296
- 全文大小：678K
- 年卷期：v.21,no.4(August 2005)
- ISSN：1520-6033
文摘
In this study, an in vitro multicellular tumor spheroid model was developed usingmicroencapsulation, and the feasibility of using the microencapsulated multicellulartumor 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 
m in diameter wasformed in the microcapsule after 5 days of cultivation. The cell morphology, proliferation, and viability of the MMTS were characterized using phase contrast microscopy,BrdU-labeling, MTT stain, calcein AM/ED-2 stain, and H&E stain. It demonstratedthat the MMTS was viable and that the proliferating cells were mainly localized tothe periphery of the cell spheroid and the apoptotic cells were in the core. The MCF-7MMTS was treated with mitomycin C (MC) at a concentration of 0.1, 1, or 10 timesthat of peak plasma concentration (ppc) for up to 72 h. The cytotoxicity wasdemonstrated clearly by the reduction in cell spheroid size and the decrease in cellviability. The MMTS was further used to screen the anticancer effect of chemotherapeutic drugs, treated with MC, adriamycin (ADM) and 5-fluorouracil (5-FU) atconcentrations of 0.1, 1, and 10 ppc for 24, 48, and 72 h. MCF-7 monolayer culturewas used as control. Similar to monolayer culture, the cell viability of MMTS wasreduced after treatment with anticancer drugs. However, the inhibition rate of cellviability in MMTS was much lower than that in monolayer culture. The MMTS wasmore resistant to anticancer drugs than monolayer culture. The inhibition rates ofcell viability were 68.1%, 45.1%, and 46.8% in MMTS and 95.1%, 86.8%, and 91.6% inmonolayer 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-FUand ADM. It demonstrated that the MMTS has the potential to be a rapid and validin vitro model to screen chemotherapeutic drugs with a feature to mimic in vivo three-dimensional (3-D) cell growth pattern.
m in diameter wasformed in the microcapsule after 5 days of cultivation. The cell morphology, proliferation, and viability of the MMTS were characterized using phase contrast microscopy,BrdU-labeling, MTT stain, calcein AM/ED-2 stain, and H&E stain. It demonstratedthat the MMTS was viable and that the proliferating cells were mainly localized tothe periphery of the cell spheroid and the apoptotic cells were in the core. The MCF-7MMTS was treated with mitomycin C (MC) at a concentration of 0.1, 1, or 10 timesthat of peak plasma concentration (ppc) for up to 72 h. The cytotoxicity wasdemonstrated clearly by the reduction in cell spheroid size and the decrease in cellviability. The MMTS was further used to screen the anticancer effect of chemotherapeutic drugs, treated with MC, adriamycin (ADM) and 5-fluorouracil (5-FU) atconcentrations of 0.1, 1, and 10 ppc for 24, 48, and 72 h. MCF-7 monolayer culturewas used as control. Similar to monolayer culture, the cell viability of MMTS wasreduced after treatment with anticancer drugs. However, the inhibition rate of cellviability in MMTS was much lower than that in monolayer culture. The MMTS wasmore resistant to anticancer drugs than monolayer culture. The inhibition rates ofcell viability were 68.1%, 45.1%, and 46.8% in MMTS and 95.1%, 86.8%, and 91.6% inmonolayer 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-FUand ADM. It demonstrated that the MMTS has the potential to be a rapid and validin vitro model to screen chemotherapeutic drugs with a feature to mimic in vivo three-dimensional (3-D) cell growth pattern.