Liposome armed with herpes virus-derived gH625 peptide to overcome doxorubicin resistance in lung adenocarcinoma cell lines

• Published in: Oncotarget 2016-01, Vol.7 (4), p.4077-4092
• Main Authors: Perillo, Emiliana, Porto, Stefania, Falanga, Annarita, Zappavigna, Silvia, Stiuso, Paola, Tirino, Virginia, Desiderio, Vincenzo, Papaccio, Gianpaolo, Galdiero, Massimiliano, Giordano, Antonio, Galdiero, Stefania, Caraglia, Michele
• Format: Article
• Language: English
• Subjects: Adenocarcinoma - drug therapy; Adenocarcinoma - metabolism; Adenocarcinoma - pathology; Antibiotics, Antineoplastic - administration & dosage; Antibiotics, Antineoplastic - chemistry; Apoptosis - drug effects; Blotting, Western; Carcinoma, Non-Small-Cell Lung - drug therapy; Carcinoma, Non-Small-Cell Lung - metabolism; Carcinoma, Non-Small-Cell Lung - pathology; Cell Proliferation - drug effects; Doxorubicin - administration & dosage; Doxorubicin - chemistry; Drug Resistance, Neoplasm - drug effects; Flow Cytometry; Humans; Liposomes - administration & dosage; Liposomes - chemistry; Lung Neoplasms - drug therapy; Lung Neoplasms - metabolism; Lung Neoplasms - pathology; Microscopy, Confocal; Oxidative Stress - drug effects; Peptides - administration & dosage; Peptides - chemistry; Research Paper; Tumor Cells, Cultured; Viral Envelope Proteins - administration & dosage; Viral Envelope Proteins - chemistry
• ISSN: 1949-2553; 1949-2553
• DOI: 10.18632/oncotarget.6013

New delivery systems including liposomes have been developed to circumvent drug resistance. To enhance the antitumor efficacy of liposomes encapsulating anti-cancer agents, we used liposomes externally conjugated to the 20 residue peptide gH625. Physicochemical characterization of the liposome system showed a size of 140 nm with uniform distribution and high doxorubicin encapsulation efficiency. We evaluated the effects of increasing concentrations of liposomes encapsulating Doxo (LipoDoxo), liposomes encapsulating Doxo conjugated to gH625 (LipoDoxo-gH625), empty liposomes (Lipo) or free Doxo on growth inhibition of either wild type (A549) or doxorubicin-resistant (A549 Dx) human lung adenocarcinoma. After 72 h, we found that the growth inhibition induced by LipoDoxo-gH625 was higher than that caused by LipoDoxo with an IC50 of 1 and 0.3 μM in A549 and A549 Dx cells, respectively. The data on cell growth inhibition were paralleled by an higher oxidative stress and an increased uptake of Doxo induced by LipoDoxo-gH625 compared to LipoDoxo, above all in A549 Dx cells. Cytometric analysis showed that the antiproliferative effects of each drug treatment were mainly due to the induction of apoptosis. In conclusion, liposomes armed with gH625 are able to overcome doxorubicin resistance in lung adenocarcinoma cell lines.