title: A tissue-engineered gastric cancer model for mechanistic study of anti-tumor drugs.
abstract: The use of the traditional xenograft subcutaneous tumor model has been contested because of its limitations, such as a slow tumorigenesis, inconsistent chemotherapeutic results, etc. In light of these challenges, we aim to revamp the traditional model by employing an electrospun scaffold composed of polydioxanone, gelatin and elastin to boost the tumorigenesis. The scaffold featured a highly porous microstructure and successfully supported the growth of tumor cells in vitro without provoking apoptosis. In vivo studies showed that in the scaffold model the tumor volume increased by 43.27% and the weight by 75.58%, respectively, within a 12-week period. In addition, the scaffold model saw an increase of CD24(+) and CD44(+) cells in the tumor mass by 42% and 313%, respectively. The scaffolding materials did not lead to phenotypic changes during the tumorigenesis. Thereafter, in the scaffold model, we found that the chemotherapeutic regimen of docetaxel, cisplatin and fluorouracil unleashed a stronger capability than the regimen comprising cisplatin and fluorouracil to deplete the CD44(+) subpopulation. This discovery sheds mechanistic lights on the role of docetaxel for its future chemotherapeutic applications. This revamped model affords cancer scientists a convenient and reliable platform to mechanistically investigate the chemotherapeutic drugs on gastric cancer stem cells.
authors.affiliation: Department of Surgery, Xinhua Hospital (Chongming), Shanghai Jiaotong University, Shanghai 202150, People's Republic of China.
authors.forename: Ming
authors.initials: M
authors.lastname: Gao
authors.forename: Yiting
authors.initials: Y
authors.lastname: Cai
authors.forename: Wei
authors.initials: W
authors.lastname: Wu
authors.forename: Yazhou
authors.initials: Y
authors.lastname: Shi
authors.forename: Zhewei
authors.initials: Z
authors.lastname: Fei
mesh_terms: D000818:Animals; D000970:Antineoplastic Agents / Q000737:chemistry*; D017209:Apoptosis; D051927:CD24 Antigen / Q000378:metabolism; D002470:Cell Survival; D002945:Cisplatin / Q000737:chemistry; D004354:Drug Screening Assays, Antitumor; D004549:Elastin / Q000737:chemistry; D005260:Female; D005472:Fluorouracil / Q000737:chemistry; D005780:Gelatin / Q000737:chemistry; D006801:Humans; D018960:Hyaluronan Receptors / Q000378:metabolism; D051379:Mice; D008807:Mice, Inbred BALB C; D008819:Mice, Nude; D014411:Neoplastic Stem Cells / Q000187:drug effects; D010641:Phenotype; D016687:Polydioxanone / Q000737:chemistry; D016062:Porosity; D013274:Stomach Neoplasms / Q000188:drug therapy* / Q000473:pathology; D013997:Time Factors; D023822:Tissue Engineering / Q000379:methods*; D054457:Tissue Scaffolds
chemical_list: D000970:Antineoplastic Agents; D051927:CD24 Antigen; D018960:Hyaluronan Receptors; D016687:Polydioxanone; D005780:Gelatin; D004549:Elastin; D002945:Cisplatin; D005472:Fluorouracil