title: Developing multi-cellular tumor spheroid model (MCTS) in the chitosan/collagen/alginate (CCA) fibrous scaffold for anticancer drug screening.
abstract: In this work, a 3D MCTS-CCA system was constructed by culturing multi-cellular tumor spheroid (MCTS) in the chitosan/collagen/alginate (CCA) fibrous scaffold for anticancer drug screening. The CCA scaffolds were fabricated by spray-spinning. The interactions between the components of the spray-spun fibers were evidenced by methods of Coomassie Blue stain, X-ray diffraction (XRD) and Fourier transform-infrared spectroscopy (FTIR). Co-culture indicated that MCF-7 cells showed a spatial growth pattern of multi-cellular tumor spheroid (MCTS) in the CCA fibrous scaffold with increased proliferation rate and drug-resistance to MMC, ADM and 5-Aza comparing with the 2D culture cells. Significant increases of total viable cells were found in 3D MCTS groups after drug administration by method of apoptotic analysis. Glucose-lactate analysis indicated that the metabolism of MCTS in CCA scaffold was closer to the tumor issue in vivo than the monolayer cells. In addition, MCTS showed the characteristic of epithelial mesenchymal transition (EMT) which is subverted by carcinoma cells to facilitate metastatic spread. These results demonstrated that MCTS in CCA scaffold possessed a more conservative phenotype of tumor than monolayer cells, and anticancer drug screening in 3D MCTS-CCA system might be superior to the 2D culture system.
authors.affiliation: Laboratory of Biomedical Material Engineering, Dalian Institute of Chemical Physics, Chinese Academy of Sciences, 457 Zhongshan Road, Dalian 116023, PR China; Affiliated General Hospital, Tianguan Group Co., Ltd, Nanyang 473000, PR China; Testing Center of Henan Tianguan Group Co., Ltd, Nanyang 473000, PR China. Electronic address: wppzheng@126.com.
authors.forename: Jian-Zheng
authors.initials: JZ
authors.lastname: Wang
authors.affiliation: Laboratory of Biomedical Material Engineering, Dalian Institute of Chemical Physics, Chinese Academy of Sciences, 457 Zhongshan Road, Dalian 116023, PR China; Affiliated General Hospital, Tianguan Group Co., Ltd, Nanyang 473000, PR China; Testing Center of Henan Tianguan Group Co., Ltd, Nanyang 473000, PR China.
authors.forename: Yu-Xia
authors.initials: YX
authors.lastname: Zhu
authors.affiliation: Affiliated General Hospital, Tianguan Group Co., Ltd, Nanyang 473000, PR China; Testing Center of Henan Tianguan Group Co., Ltd, Nanyang 473000, PR China.
authors.forename: Hui-Chao
authors.initials: HC
authors.lastname: Ma
authors.affiliation: Affiliated General Hospital, Tianguan Group Co., Ltd, Nanyang 473000, PR China; Testing Center of Henan Tianguan Group Co., Ltd, Nanyang 473000, PR China.
authors.forename: Si-Nan
authors.initials: SN
authors.lastname: Chen
authors.affiliation: Affiliated General Hospital, Tianguan Group Co., Ltd, Nanyang 473000, PR China; Testing Center of Henan Tianguan Group Co., Ltd, Nanyang 473000, PR China.
authors.forename: Ji-Ye
authors.initials: JY
authors.lastname: Chao
authors.affiliation: Affiliated General Hospital, Tianguan Group Co., Ltd, Nanyang 473000, PR China; Testing Center of Henan Tianguan Group Co., Ltd, Nanyang 473000, PR China.
authors.forename: Wen-Ding
authors.initials: WD
authors.lastname: Ruan
authors.affiliation: Affiliated General Hospital, Tianguan Group Co., Ltd, Nanyang 473000, PR China; Testing Center of Henan Tianguan Group Co., Ltd, Nanyang 473000, PR China.
authors.forename: Duo
authors.initials: D
authors.lastname: Wang
authors.affiliation: Affiliated General Hospital, Tianguan Group Co., Ltd, Nanyang 473000, PR China; Testing Center of Henan Tianguan Group Co., Ltd, Nanyang 473000, PR China.
authors.forename: Feng-guang
authors.initials: FG
authors.lastname: Du
authors.affiliation: State Key Laboratory of Optoelectronic Materials and Technologies, Sun Yat-sen University, Guangzhou 510275, PR China.
authors.forename: Yue-Zhong
authors.initials: YZ
authors.lastname: Meng
mesh_terms: D000464:Alginates / Q000737:chemistry*; D000970:Antineoplastic Agents / Q000633:toxicity; D001374:Azacitidine / Q000633:toxicity; D018929:Cell Culture Techniques / Q000295:instrumentation / Q000379:methods; D049109:Cell Proliferation / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D048271:Chitosan / Q000737:chemistry*; D018920:Coculture Techniques; D004317:Doxorubicin / Q000633:toxicity; D004354:Drug Screening Assays, Antitumor; D058750:Epithelial-Mesenchymal Transition / Q000187:drug effects; D020723:Glucuronic Acid / Q000737:chemistry; D006603:Hexuronic Acids / Q000737:chemistry; D006801:Humans; D061986:MCF-7 Cells; D008855:Microscopy, Electron, Scanning; D008856:Microscopy, Fluorescence; D016685:Mitomycin / Q000633:toxicity; D017550:Spectroscopy, Fourier Transform Infrared; D018874:Spheroids, Cellular / Q000166:cytology; D014961:X-Ray Diffraction
chemical_list: D000464:Alginates; D000970:Antineoplastic Agents; D006603:Hexuronic Acids; D016685:Mitomycin; D004317:Doxorubicin; D020723:Glucuronic Acid; D048271:Chitosan; D001374:Azacitidine
keywords: Chitosan/collagen/alginate scaffold (CCA); Multi-cellular tumor spheroid (MCTS); Spray-spinning; Three-dimensional cell culture