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 mum 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-labeling, 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.