title: Cell-like features imprinted in the physical nano- and micro-topography of the environment modify the responses to anti-cancer drugs of endometrial cancer cells.
abstract: Topographical features of cells at nanometre resolution were fabricated in polystyrene. The study investigated the effect of physical topography on the response of cancer cells to the common anticancer drugs, paclitaxel and doxorubicin. Human endometrial cancer cells (Ishikawa) were incubated on substrates containing cell-like features that had been fabricated using our bioimprint methodology to create moulds of cells with positive (convex) and negative (concave) topography. Control cultures were performed on flat substrates. Effects of the drugs on caspase-3 expression, proliferating nuclear antigen (PCNA) expression, cell number and vascular endothelial growth factor (VEGF) secretion were determined. Results revealed that the topography influenced the cell responses in a drug-dependent manner i.e. paclitaxel effects were sensitive to topography differently to those of doxorubicin. In addition, function signalling pathways were sensitive to the detailed topography i.e. positive imprint and negative imprint induced distinct response patterns. The results in this study show for the first time that a culture surface with cell-like topography, that has both nano- and micro-resolution, influences endometrial cancer cell responses to chemotherapy drugs. The effects are dependent on the topography and also on the chemotherapy drug. In particular, the platforms described have potential to provide substrates with high physical relevancy on which to undertake preclinical testing of new drugs. The method also allows for use of different cell types to provide cell-specific topography. The results imply that physical architecture of the cancer cell environment may be a suitable prospective target to enhance clinical activity of traditional drugs. Additionally or alternatively we provide compelling support for the notion that understanding the physical component of the nano- and micro-environment may encourage a redirection of drug development. Further, our observation that the cells distinguish between the different cell-like topographies (positive and negative bioimprints) indicates that a realistic topography is advantageous as growth platforms in experiment design.
authors.affiliation: Department of Obstetrics and Gynaecology, University of Otago Christchurch, 2 Riccarton Avenue, Christchurch, New Zealand. MacDiarmid Institute of Advanced Materials and Nanotechnology Christchurch, New Zealand.
authors.forename: Li Hui
authors.initials: LH
authors.lastname: Tan
authors.forename: Peter H
authors.initials: PH
authors.lastname: Sykes
authors.forename: Maan M
authors.initials: MM
authors.lastname: Alkaisi
authors.forename: John J
authors.initials: JJ
authors.lastname: Evans
mesh_terms: D000970:Antineoplastic Agents / Q000494:pharmacology* / Q000627:therapeutic use; D062028:Bioprinting; D053148:Caspase 3 / Q000378:metabolism; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects*; D004317:Doxorubicin / Q000494:pharmacology / Q000627:therapeutic use; D016889:Endometrial Neoplasms / Q000188:drug therapy / Q000473:pathology; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D006801:Humans; D008855:Microscopy, Electron, Scanning; D049329:Nanostructures / Q000737:chemistry*; D017239:Paclitaxel / Q000494:pharmacology / Q000627:therapeutic use; D011137:Polystyrenes / Q000737:chemistry; D018809:Proliferating Cell Nuclear Antigen / Q000378:metabolism; D013499:Surface Properties; D042461:Vascular Endothelial Growth Factor A / Q000032:analysis
chemical_list: D000970:Antineoplastic Agents; D011137:Polystyrenes; D018809:Proliferating Cell Nuclear Antigen; D042461:Vascular Endothelial Growth Factor A; D004317:Doxorubicin; D053148:Caspase 3; D017239:Paclitaxel