| Summary: | 碩士 === 高雄醫學大學 === 臨床醫學研究所 === 104 === Lung cancers become most terrible result of cancer-related death in Taiwan. Most cases get metastatic conditions in diagnostic time. Bone is one most common metastatic site. There is no specific study that investigates association between bone metastasis and benzo(a)pyrene (BaP) that is well known carcinogen in lung cancer. Human non-small cell lung cancer cell line H460 were increased production of parathyroid hormone-related protein (PTHrP) and IL-8 that were tumor-derived factor for bone metastasis after BaP treatment. Expression of IL-8 was influenced by upregulation of PTHrP in BaP-treated H460 cell line. Production of osteoclastogenesis activators, including macrophage colony-stimulating factor (M-CSF) and receptor activator of nuclear factor κB ligand (RANKL) were increased and the inhibitor, osteoprotegerin (OPG) was decreased in osteoblasts that was treated by BaP-treated H460 condition medium. Therefore, osteoclast differentiation and bone resorption were increased. Tricetin (TCN), a dietary flavonoid, reversed BaP-mediated osteoclastogenesis.
In conclusion, BaP in human non-small cell lung cancer increased production of PTHrP. PTHrP upregulated expression of IL-8. Above situations increased activity of osteoclastogenesis through increased production of M-CSF and RANKL, decreased production of OPG in osteoblasts. This is first study for role of well known carcinogen BaP in non-small cell lung cancer bone metastasis. TCN is potentially effective for treatment of BaP related non-small cell lung cancer bone metastasis.
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