RT Journal Article
T1 5-Fluorouracil-loaded poly(ε-caprolactone) nanoparticles combined with phage E gene therapy as a new strategy against colon cancer
A1 Ortiz, Raúl
A1 Prados, José
A1 Melguizo, Consolación
A1 Arias, José L
A1 Ruiz, M Adolfina
A1 Alvarez, Pablo J
A1 Caba, Octavio
A1 Luque, Raquel
A1 Segura, Ana
A1 Aránega, Antonia
K1 colon cancer
K1 combined therapy
K1 5-fluorouracil
K1 gene therapy
K1 E gene
K1 poly (ε-caprolactone)
K1 Neoplasias del Colon
K1 Terapia de Gen
K1 Humanos
K1 Fluorouracilo
K1 Nanopartículas
K1 Antineoplásicos
K1 Apoptosis
AB This work aimed to develop a new therapeutic approach to increase the efficacy of 5-fluorouracil (5-FU) in the treatment of advanced or recurrent colon cancer. 5-FU-loaded biodegradable poly(ε-caprolactone) nanoparticles (PCL NPs) were combined with the cytotoxic suicide gene E (combined therapy). The SW480 human cancer cell line was used to assay the combined therapeutic strategy. This cell line was established from a primary adenocarcinoma of the colon and is characterized by an intrinsically high resistance to apoptosis that correlates with its resistance to 5-FU. 5-FU was absorbed into the matrix of the PCL NPs during synthesis using the interfacial polymer disposition method. The antitumor activity of gene E from the phage ϕX174 was tested by generating a stable clone (SW480/12/E). In addition, the localization of E protein and its activity in mitochondria were analyzed. We found that the incorporation of 5-FU into PCL NPs (which show no cytotoxicity alone), significantly improved the drug's anticancer activity, reducing the proliferation rate of colon cancer cells by up to 40-fold when compared with the nonincorporated drug alone. Furthermore, E gene expression sensitized colon cancer cells to the cytotoxic action of the 5-FU-based nanomedicine. Our findings demonstrate that despite the inherent resistance of SW480 to apoptosis, E gene activity is mediated by an apoptotic phenomenon that includes modulation of caspase-9 and caspase-3 expression and intense mitochondrial damage. Finally, a strongly synergistic antiproliferative effect was observed in colon cancer cells when E gene expression was combined with the activity of the 5-FU-loaded PCL NPs, thereby indicating the potential therapeutic value of the combined therapy.
PB Dove Medical Press
SN 1176-9114
YR 2012
FD 2012-01-06
LK http://hdl.handle.net/10668/569
UL http://hdl.handle.net/10668/569
LA en
NO Ortiz R, Prados J, Melguizo C, Arias JL, Ruiz MA, Álvarez PJ, et al. 5-Fluorouracil-loaded poly(ε-caprolactone) nanoparticles combined with phage E gene therapy as a new strategy against colon cancer. Int J Nanomedicine. 2012;7:95-107
NO Original research
DS RISalud
RD Apr 11, 2025