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        Inhibition of Tumor Growth by Recombinant Adenovirus Containing Human Lactoferrin through Inducing Tumor Cell Apoptosis in Mice Bearing EMT6 Breast Cancer

        Jianjie Wang,Qingwang Li,Yetao Ou,Zengsheng Han,Kun Li,Peijun Wang,Shaobo Zhou 대한약학회 2011 Archives of Pharmacal Research Vol.34 No.6

        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 adrhLTF might be a promising drug for breast cancer gene therapy.

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