Endocrine Abstracts

Cigarette smoke contains over 60 well established carcinogens. There are strong links between some of these carcinogens and various types of smoking-induced cancers. In this study we investigated whether cigarette smoke extracts (CSEs) affects the cell proliferation, migration, and invasion of BG-1 human ovarian cancer cells by alteration of epithelial-mesenchymal transition (EMT). We confirmed that CSEs increased the ovarian cancer cell viability in a dose-dependent manner. Also the protein expression of cyclin D1 and cyclin E1 was increased while p21 and p27 expression was decreased by treatment of all CSEs (3R4F and two-domestic commercial cigarettes). Additionally the alteration of EMT markers such as E-cadherian and N-cadherin was examined. The expression of E-cadherin was reduced by the treatment of CSEs while its reverse transition marker N-cadherin was increased. EMT-associated transcriptional factors, Snail and Slug were also up-regulated by CSEs treatment. These results indicate that CSEs can increase EMT process in BG-1 ovarian cancer cells, which is associated with cancer cell migration. We examined the migration activity through scratch assay and fibronectin coated trans-well invasion assay, in which CSEs increased cancer cell migratory propensity. These functional alterations were associated with changes in the metastasis-related genes. Upon CSEs stimulation, the expression of MMP-9 and cathepsin D was increased. Taken together, we confirmed that CSEs increased the growth of human ovarian cancer cells and the development of metastasis by stimulating cell cycle and EMT process through up- and down-regulation of a multiple cellular markers and signaling proteins and that CSEs exposure might have a higher risk of ovarian cancer than nonsmokers. Based on the results of this in vitro study, we will examine the in vivo risk assessment of CSEs in a xenografted mouse model transplanted with BG-1 human ovarian cancer cells.