title: Bovine lactoferrin inhibits lung cancer growth through suppression of both inflammation and expression of vascular endothelial growth factor.
abstract: Lung cancers are among the most common cancers in the world, and the search for effective and safe drugs for the chemoprevention and therapy of pulmonary cancer has become important. In this study, bovine lactoferrin (bLF) was used in both in vitro and in vivo approaches to investigate its activity against lung cancer. A human lung cancer cell line, A549, which expresses a high level of vascular endothelial growth factor (VEGF) under hypoxia, was used as an in vitro system for bLF treatment. A strain of transgenic mice carrying the human VEGF-A165 (hVEGF-A165) gene, which induces pulmonary tumors, was used as an in vivo lung cancer therapy model. We found that bLF significantly decreased proliferation of A549 cells by decreasing the expression of VEGF protein in a dose-dependent manner. Furthermore, oral administration of bLF at 300 mg/kg of body weight 3 times a week for 1.5 mo to the transgenic mice overexpressing hVEGF-A165 significantly eliminated expression of hVEGF-A165 and suppressed the formation of tumors. Additionally, treatment with bLF significantly decreased the levels of proinflammatory cytokines, such as tumor necrosis factor-α, and antiinflammatory cytokines, such as IL-4 and IL-10. Levels of IL-6, which is both a proinflammatory and an antiinflammatory cytokine, were also reduced. Treatment with bLF decreased levels of tumor necrosis factor-α, IL-4, IL-6, and IL-10 cytokines, resulting in limited inflammation, which then restricted growth of the lung cancer. Our results revealed that bLF is an inhibitor of angiogenesis and blocks lung cell inflammation; as such, it has considerable potential for therapeutic use in the treatment of lung cancer.
authors: Department of Life Sciences, Agricultural Biotechnology Center, National Chung Hsing University, Taichung 402, Taiwan.
authors: Yu-Tang
authors: YT
authors: Tung
authors: Department of Bioresources and Molecular Biotechnology, Da-Yeh University, Changhwa 515, Taiwan.
authors: Hsiao-Ling
authors: HL
authors: Chen
authors: Department of Life Sciences, Agricultural Biotechnology Center, National Chung Hsing University, Taichung 402, Taiwan; Department of Internal Medicine, China Medical University, Taichung 404, Taiwan.
authors: Chih-Ching
authors: CC
authors: Yen
authors: Department of Surgery, National Taiwan University Hospital Yun-Lin Branch, Yun-Lin 640, Taiwan.
authors: Po-Ying
authors: PY
authors: Lee
authors: Department of Life Sciences, Agricultural Biotechnology Center, National Chung Hsing University, Taichung 402, Taiwan; Taichung Hospital, Department of Health, Taichung 403, Taiwan.
authors: Hsin-Chung
authors: HC
authors: Tsai
authors: Department of Life Sciences, Agricultural Biotechnology Center, National Chung Hsing University, Taichung 402, Taiwan; Taichung Hospital, Department of Health, Taichung 403, Taiwan.
authors: Ming-Fong
authors: MF
authors: Lin
authors: Department of Life Sciences, Agricultural Biotechnology Center, National Chung Hsing University, Taichung 402, Taiwan. Electronic address: chchen1@dragon.nchu.edu.tw.
authors: Chuan-Mu
authors: CM
authors: Chen
mesh_terms: D020533:Angiogenesis Inhibitors; D000818:Animals; D000893:Anti-Inflammatory Agents / Q000494:pharmacology*; D000970:Antineoplastic Agents; D002417:Cattle; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D016207:Cytokines / Q000037:antagonists & inhibitors; D015870:Gene Expression / Q000187:drug effects; D006801:Humans; D015850:Interleukin-6 / Q000235:genetics; D007781:Lactoferrin / Q000494:pharmacology* / Q000627:therapeutic use; D008175:Lung Neoplasms / Q000473:pathology*; D051379:Mice; D008822:Mice, Transgenic; D010446:Peptide Fragments / Q000235:genetics; D012333:RNA, Messenger / Q000032:analysis; D014409:Tumor Necrosis Factor-alpha / Q000235:genetics; D042461:Vascular Endothelial Growth Factor A / Q000032:analysis / Q000037:antagonists & inhibitors* / Q000235:genetics
chemical_list: D020533:Angiogenesis Inhibitors; D000893:Anti-Inflammatory Agents; D000970:Antineoplastic Agents; D016207:Cytokines; D015850:Interleukin-6; D010446:Peptide Fragments; D012333:RNA, Messenger; D014409:Tumor Necrosis Factor-alpha; D042461:Vascular Endothelial Growth Factor A; C511613:vascular endothelial growth factor A (138-165); D007781:Lactoferrin