Aptamer targeting of the elongation factor 1A impairs hepatocarcinoma cells viability and potentiates bortezomib and idarubicin effects.
The high morbidity and mortality of hepatocellular carcinoma (HCC) is mostly due to the limited efficacy of the available therapeutic approaches. Here we explore the anti-HCC potential of an aptamer targeting the elongation factor 1A (eEF1A), a protein implicated in the promotion of HCC. As delivery methods, we have compared the effectiveness of cationic liposome and cholesterol-mediated approaches. A75 nucleotide long aptamer containing GT repetition (GT75) was tested in three HCC cell lines, HepG2, HuH7 and JHH6. When delivered by liposomes, GT75 was able to effectively reducing HCC cells viability in a dose and time dependent fashion. Particular sensitive were JHH6 where increased apoptosis with no effects on cell cycle were observed. GT75 effect was likely due to the interference with eEF1A activity as neither the mRNA nor the protein levels were significantly affected. Notably, cholesterol-mediated delivery of GT75 abrogated its efficacy due to cellular mis-localization as proven by fluorescence and confocal microscopic analysis. Finally, liposome-mediated delivery of GT75 improved the therapeutic index of the anticancer drugs bortezomib and idarubicin. In conclusion, liposome but not cholesterol-mediated delivery of GT75 resulted in an effective delivery of GT75, causing the impairment of the vitality of a panel of HCC derived cells.
Department of Life Sciences, University of Trieste, Italy.
Bruna
B
Scaggiante
Department of Industrial Engineering and Information Technology, University of Trieste, Italy.
Rosella
R
Farra
Department of Life Sciences, University of Trieste, Italy.
Barbara
B
Dapas
Department of Life Sciences, University of Trieste, Italy.
Gabriele
G
Baj
Department of Medical, Surgery and Health Sciences, University of Trieste, Cattinara Hospital, Italy.
Gabriele
G
Pozzato
Department of Industrial Engineering and Information Technology, University of Trieste, Italy.
Mario
M
Grassi
Department of Medical, Surgery and Health Sciences, University of Trieste, Cattinara Hospital, Italy.
Fabrizio
F
Zanconati
Department of Life Sciences, University of Trieste, Italy. Electronic address: ggrassi@units.it.
Gabriele
G
Grassi
D000970:Antineoplastic Agents / Q000008:administration & dosage / Q000494:pharmacology; D017209:Apoptosis / Q000187:drug effects; D052157:Aptamers, Nucleotide / Q000008:administration & dosage; D000069286:Bortezomib / Q000008:administration & dosage* / Q000494:pharmacology; D006528:Carcinoma, Hepatocellular / Q000188:drug therapy* / Q000473:pathology; D045744:Cell Line, Tumor; D002470:Cell Survival / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D016503:Drug Delivery Systems; D056945:Hep G2 Cells; D006801:Humans; D015255:Idarubicin / Q000008:administration & dosage* / Q000494:pharmacology; D008081:Liposomes; D008113:Liver Neoplasms / Q000188:drug therapy* / Q000473:pathology; D018613:Microscopy, Confocal; D008856:Microscopy, Fluorescence; D020648:Peptide Elongation Factor 1 / Q000378:metabolism; D013997:Time Factors
D000970:Antineoplastic Agents; D052157:Aptamers, Nucleotide; C094814:EEF1A1 protein, human; D008081:Liposomes; D020648:Peptide Elongation Factor 1; D000069286:Bortezomib; D015255:Idarubicin
Aptamer; Cholesterol-delivery; HCC; Liposome-delivery; eEF1A