Data di Pubblicazione:
2014
Citazione:
Giant lysosomes as a chemotherapy resistance mechanism in hepatocellular carcinoma cells / F. Colombo, E. Trombetta, P. Cetrangolo, M. Maggioni, P. Razini, F. De Santis, Y. Torrente, D. Prati, E. Torresani, L. Porretti. - In: PLOS ONE. - ISSN 1932-6203. - 9:12(2014 Dec 10), pp. e114787.-e114787.1.
Abstract:
Despite continuous improvements in therapeutic protocols, cancer-related mortality
is still one of the main problems facing public health. The main cause of treatment
failure is multi-drug resistance (MDR: simultaneous insensitivity to different anticancer
agents), the underlying molecular and biological mechanisms of which
include the activity of ATP binding cassette (ABC) proteins and drug
compartmentalisation in cell organelles. We investigated the expression of the main
ABC proteins and the role of cytoplasmic vacuoles in the MDR of six hepatocellular
carcinoma (HCC) cell lines, and confirmed the accumulation of the yellow anticancer
drug sunitinib in giant (four lines) and small cytoplasmic vacuoles of
lysosomal origin (two lines). ABC expression analyses showed that the main ABC
protein harboured by all of the cell lines was PGP, whose expression was not
limited to the cell membrane but was also found on lysosomes. MTT assays
showed that the cell lines with giant lysosomes were more resistant to sorafenib
treatment than those with small lysosomes (p,0.01), and that verapamil incubation
can revert this resistance, especially if it is administered after drug pre-incubation.
The findings of this study demonstrate the involvement of PGP-positive lysosomes
in drug sequestration and MDR in HCC cell lines. The possibility of modulating this
mechanism using PGP inhibitors could lead to the development of new targeted
strategies to enhance HCC treatment.
Tipologia IRIS:
01 - Articolo su periodico
Keywords:
multidrug-resistance; drug-resistance; transporter; verapamil; cancer; chemoresistance; sequestration; inhibition; metabolism
Elenco autori:
F. Colombo, E. Trombetta, P. Cetrangolo, M. Maggioni, P. Razini, F. De Santis, Y. Torrente, D. Prati, E. Torresani, L. Porretti
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