期刊
BIOTECHNOLOGY LETTERS
卷 38, 期 8, 页码 1389-1395出版社
SPRINGER
DOI: 10.1007/s10529-016-2035-1
关键词
Anti-cancer drugs; Cancer spheroids; Drug screening; Perfusion; Three-dimensional cancer model
资金
- Biotechnology and Biological Science Research Council (BBSRC), UK
- BBSRC [BB/L003961/1] Funding Source: UKRI
- EPSRC [EP/H021442/1] Funding Source: UKRI
- Biotechnology and Biological Sciences Research Council [BB/L003961/1] Funding Source: researchfish
- Engineering and Physical Sciences Research Council [EP/H021442/1] Funding Source: researchfish
To build an in vitro-perfused, three-dimensional (3D) spheroid model based on the TissueFlex system for anti-cancer drug efficacy testing in order to mimic avascular micro-tissues with inherent O-2, nutrient and metabolite gradients, and to provide a more accurate prediction of drug toxicity and efficacy than traditional in vitro tumour models in conventional static culture well plates. The perfused cancer spheroid model showed higher cell viability and increased diameter of spheroids over a relatively long culture period (17 days). Three anti-cancer drugs with different cytotoxic mechanisms were tested. In perfusion, lower cytotoxicity was observed for traditional cytotoxic drug 5-fluorouracil and microtubule-interfering, paclitaxel, showed greater interruption of spheroid integrity. For the hypoxic-dependent drug, tirapazamine, there was no significant difference observed between static and perfusion cultures. The perfusion culture provides a better homeostasis for cancer cell growth in a more controllable working platform for long-term drug testing.
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