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KMID : 0043320110340060897
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Archives of Pharmacal Research
2011 Volume.34 No. 6 p.897 ~ p.995
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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
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Wang Jianjie
Li Qingwang
Ou Yetao
Han Zengsheng
Li Kun
Wang Peijun
Zhou Shaobo
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Abstract
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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 (108 and 5 × 108 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.
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KEYWORD
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Lactoferrin, Adenovirus vector, Gene therapy, Breast cancer, Apoptosis, Pathway
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