Inhibition of tumor growth by recombinant adenovirus containing human lactoferrin through inducing tumor cell apoptosis in mice bearing EMT6 breast cancer

• Published in: Archives of pharmacal research Vol. 34; no. 6; pp. 987 - 995
• Main Authors: Wang, Jianjie, Li, Qingwang, Ou, Yetao, Han, Zengsheng, Li, Kun, Wang, Peijun, Zhou, Shaobo
• Format: Journal Article
• Language: English
• Published: Heidelberg Pharmaceutical Society of Korea 01.06.2011; 대한약학회
• Subjects: Adenoviridae - genetics; Animals; Apoptosis; Blotting, Western; Breast Neoplasms - pathology; Breast Neoplasms - therapy; Caspase 3 - metabolism; DNA, Complementary; Female; Flow Cytometry; Genetic Therapy - methods; Genetic Vectors; HEK293 Cells; Humans; In Situ Nick-End Labeling; Lactoferrin - administration & dosage; Lactoferrin - pharmacology; Medicine; Mice; Pharmacology/Toxicology; Pharmacy; Reverse Transcriptase Polymerase Chain Reaction; 약학; Lactoferrin; Breast cancer; Gene therapy; Adenovirus vector; Pathway; Apoptosis
• ISSN: 0253-6269; 1976-3786
• DOI: 10.1007/s12272-011-0616-z

Human lactoferrin (hLTF), an 80-kDa iron-binding glycoprotein, has antitumor activity. In this study, a recombinant adenovirus containing the human lactoferrin cDNA (ad-rhLTF) was constructed and its effect on tumor growth was investigated in mice bearing EMT6 breast cancer. Ad-rhLTF was injected seven times within 14 days into the tumor site at two concentrations (10 8 and 5 × 10 8 pfu/mL) in mice bearing EMT6 breast cancer. Injected ad-rhLTF had considerable cytotoxicity on mice breast cancer, and significantly reducing the weight of tumor produced and increasing the tumor inhibition rate up to 52.64%. The presence of apoptotic cells was confirmed using TUNEL staining and flow cytometry assays. At the same time, RTPCR and Western blot analyses demonstrated that ad-rhLTF also decreased expression of Bcl-2 and increased Bax and caspase 3 expressions. Therefore, we conclude that ad-rhLTF inhibits tumor growth by inducing tumor cell apoptosis in mice with breast cancer by triggering the mitochondrial-dependent pathway and activation of caspase 3. The results indicate that ad-rhLTF might be a promising drug for breast cancer gene therapy.