title: Impact of multicellular tumor spheroids as an in vivo‑like tumor model on anticancer drug response.
abstract: The incidence of colorectal cancer is higher in men than in women, amounting to 15% of cancer-related diseases as a whole. As such, undesirable effects, arising from the administration of current chemotherapeutic agents (the FOLFIRI/FOLFOX combinations), which are exerted on the remaining non-cancerous tissues and/or cells, have contributed to the occurrence of resistance to multiple drugs, thus markedly reducing their efficacy. However, the delivery of chemotherapeutic agents may be improved and their action may be more selectively targeted to diseased tissues/cells by means of developing biotechnologies and nano‑techniques. Thus, the current focus is on creating biological tissue and related tumor models, by means of three‑dimensional (3D) spheres, in an attempt to bridge the gap between results obtained in the pre‑clinical phase and promising outcomes obtained in clinical trials. For this purpose, the characterization and use of so‑called 'multicellular tumor spheroids', may prove to be invaluable. In this study, we focus on describing the efficacy of a model 3D system as compared to the traditional 2D tumor spheres in determining drug response, highlighting a potentially greater effect of the drugs following the encapsulation of respective liposomes. The results obtained demonstrate the successful preparation of a suspension of liposomes loaded with folinic acid, oxaliplatin and 5‑fluorouracil (5‑FU), and loaded with meso‑tetra (4‑sulfonatophenyl) porphyrin. Following its use on HT‑29 colorectal cancer cells, an important comparative reduction was noted in the viability of the HT‑29 cells, demonstrating the efficacy of multicellular tumor spheroids carrying liposomes loaded with therapeutic drugs. These findings indicate that the method of drug encapsulation in liposomes may improve the treatment efficacy of chemotherapeutic agents.
authors.affiliation: Department of Biochemistry and Molecular Biology, University of Bucharest, Bucharest 050095, Romania.
authors.forename: Bianca
authors.initials: B
authors.lastname: Galateanu
authors.affiliation: Department of Biochemistry and Molecular Biology, University of Bucharest, Bucharest 050095, Romania.
authors.forename: Ariana
authors.initials: A
authors.lastname: Hudita
authors.affiliation: Department of Toxicology, Faculty of Pharmacy, 'Carol Davila' University of Medicine and Pharmacy, Bucharest 020956, Romania.
authors.forename: Carolina
authors.initials: C
authors.lastname: Negrei
authors.affiliation: National Institute of Research and Development for Chemistry and Petrochemistry ‑ ICECHIM, Bucharest 060021, Romania.
authors.forename: Rodica-Mariana
authors.initials: RM
authors.lastname: Ion
authors.affiliation: Department of Biochemistry and Molecular Biology, University of Bucharest, Bucharest 050095, Romania.
authors.forename: Marieta
authors.initials: M
authors.lastname: Costache
authors.affiliation: Department of Toxicology, Faculty of Pharmacy, 'Carol Davila' University of Medicine and Pharmacy, Bucharest 020956, Romania.
authors.forename: Miriana
authors.initials: M
authors.lastname: Stan
authors.affiliation: Department of Anatomy-Histology-Embryology, Medical School, University of Crete, Heraklion 71003, Greece.
authors.forename: Dragana
authors.initials: D
authors.lastname: Nikitovic
authors.affiliation: Michigan State University, East Lansing, MI 48824, USA.
authors.forename: A Wallace
authors.initials: AW
authors.lastname: Hayes
authors.affiliation: Laboratory of Clinical Virology, University of Crete Medical School, Heraklion 71409, Greece.
authors.forename: Demetrios A
authors.initials: DA
authors.lastname: Spandidos
authors.affiliation: Department of Forensic Sciences and Toxicology, Medical School, University of Crete, Heraklion 71003, Greece.
authors.forename: Aristidis M
authors.initials: AM
authors.lastname: Tsatsakis
authors.affiliation: Department of Surgery, 'Sf. Ioan' Emergency Clinical Hospital, 'Carol Davila' University of Medicine and Pharmacy, Bucharest 042122, Romania.
authors.forename: Octav
authors.initials: O
authors.lastname: Ginghina
mesh_terms: D000230:Adenocarcinoma / Q000188:drug therapy* / Q000473:pathology*; D000970:Antineoplastic Agents / Q000008:administration & dosage / Q000494:pharmacology*; D003110:Colonic Neoplasms / Q000188:drug therapy* / Q000473:pathology*; D004354:Drug Screening Assays, Antitumor / Q000379:methods*; D005472:Fluorouracil / Q000008:administration & dosage / Q000494:pharmacology; D005492:Folic Acid / Q000008:administration & dosage / Q000494:pharmacology; D019073:HT29 Cells; D006801:Humans; D008081:Liposomes / Q000008:administration & dosage; D009944:Organoplatinum Compounds / Q000008:administration & dosage / Q000494:pharmacology; D000077150:Oxaliplatin; D013053:Spectrophotometry; D018874:Spheroids, Cellular
chemical_list: D000970:Antineoplastic Agents; D008081:Liposomes; D009944:Organoplatinum Compounds; D000077150:Oxaliplatin; D005492:Folic Acid; D005472:Fluorouracil