Dataset Information

Three-dimensional perfused tumour spheroid model for anti-cancer drug screening.

ABSTRACT:

Objective

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 O2, 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.

Results

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.

Conclusion

The perfusion culture provides a better homeostasis for cancer cell growth in a more controllable working platform for long-term drug testing.

SUBMITTER: Wan X

PROVIDER: S-EPMC4942491 | biostudies-literature | 2016 Aug

REPOSITORIES: biostudies-literature

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Publications

Three-dimensional perfused tumour spheroid model for anti-cancer drug screening.

Wan Xiao X Li Zhaohui Z Ye Hua H Cui Zhanfeng Z

Biotechnology letters 20160511 8

<h4>Objective</h4>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 O2, 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.<h4>Results</h4>The perfused cancer spheroid model showed higher cell viability and increased ...[more]

PMID: 27167883

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Project description:Despite remarkable efforts, metastatic melanoma (MM) still presents with significant mortality. Recently, mono-chemotherapies are increasingly replenished by more cancer-specific combination therapies involving death ligands and drugs interfering with cell signaling. Still, MM remains a fatal disease because tumors rapidly develop resistance to novel therapies thereby regaining tumorigenic capacity. Although genetically engineered mouse models for MM have been developed, at present no model is available that reliably mimics the human disease and is suitable for studying mechanisms of therapeutic obstacles including cell death resistance. To improve the increasing requests on new therapeutic alternatives, reliable human screening models are demanded that translate the findings from basic cellular research into clinical applications. By developing an organotypic full skin equivalent, harboring melanoma tumor spheroids of defined sizes we have invented a cell-based model that recapitulates both the 3D organization and multicellular complexity of an organ/tumor in vivo but at the same time accommodates systematic experimental intervention. By extending our previous findings on melanoma cell sensitization toward TRAIL (tumor necrosis factor-related apoptosis-inducing ligand) by co-application of sublethal doses of ultraviolet-B radiation (UVB) or cisplatin, we show significant differences in the therapeutical outcome to exist between regular two-dimensional (2D) and complex in vivo-like 3D models. Of note, while both treatment combinations killed the same cancer cell lines in 2D culture, skin equivalent-embedded melanoma spheroids are potently killed by TRAIL+cisplatin treatment but remain almost unaffected by the TRAIL+UVB combination. Consequently, we have established an organotypic human skin-melanoma model that will facilitate efforts to improve therapeutic outcomes for malignant melanoma by providing a platform for the investigation of cytotoxic treatments and tailored therapies in a more physiological setting.

Dataset Information

Three-dimensional perfused tumour spheroid model for anti-cancer drug screening.

Objective

Results

Conclusion

Publications

Three-dimensional perfused tumour spheroid model for anti-cancer drug screening.

Similar Datasets

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