Anti-tumor activity of fenretinide complexed with human serum albumin in lung cancer xenograft mouse model

• Published in: Oncotarget Vol. 5; no. 13; pp. 4811 - 4820
• Main Authors: Durante, Sandra, Orienti, Isabella, Teti, Gabriella, Salvatore, Viviana, Focaroli, Stefano, Tesei, Anna, Pignatta, Sara, Falconi, Mirella
• Format: Journal Article
• Language: English
• Published: United States Impact Journals LLC 15.07.2014
• Subjects: Animals; Antineoplastic Agents - chemistry; Antineoplastic Agents - pharmacology; Apoptosis - drug effects; Caveolin 1 - genetics; Caveolin 1 - metabolism; Cell Line, Tumor; Coenzyme A Ligases - genetics; Coenzyme A Ligases - metabolism; Female; Fenretinide - chemistry; Fenretinide - pharmacology; Gene Expression Regulation, Neoplastic - drug effects; Humans; Immunohistochemistry; In Situ Nick-End Labeling; Lung Neoplasms - drug therapy; Lung Neoplasms - genetics; Lung Neoplasms - metabolism; Mice, Nude; Research Paper; Reverse Transcriptase Polymerase Chain Reaction; Serum Albumin - chemistry; Serum Albumin - pharmacology; Tumor Burden - drug effects; Xenograft Model Antitumor Assays
• ISSN: 1949-2553; 1949-2553
• DOI: 10.18632/oncotarget.2038

Sufficient knowledge regarding cellular and molecular basis of lung cancer progression and metastasis would help in the development of novel and effective strategies for the treatment of lung cancer. 4HPR is a synthetic retinoid with potential anti-tumor activity but is still limited because of its poor bioavailability. The use of albumin as a complexing agent for a hydrophobic drug is expected to improve the water solubility and consequently their bioavailability.This study investigated the antitumor activity of a novel complex between albumin and 4-HPR in a mouse model of human lung cancer and focuses on role and mechanism of Cav-1 mainly involved in regulating cancer and ACSVL3 mainly connected with tumor growth. Their expressions were assayed by immunohistochemistry and qRT-PCR, to demonstrate the reduction of the tumor growth following the drug treatment. Our results showed a high antitumor activity of 4HPR-HSA by reduction of the volume of tumor mass and the presence of a high level of apoptotic cell by TUNEL assay. The downregulation of Cav-1 and ACSVL3 suggested a reduction of tumor growth. In conclusion, we demonstrated the great potential of 4HPR-HSA in the treatment of lung cancer. More data about the mechanism of drug delivery the 4HPR-HSA are necessary.