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abstract:
Effects of cigarette smoke extracts on the progression and metastasis of human ovarian cancer cells via regulating epithelial-mesenchymal transition
Highlights
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- Cigarette smoke extracts (CSEs) increased ovarian cancer cell proliferation.
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- CSEs increased the migratory and invasive propensity of ovarian cancer cells.
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- CSEs regulated the protein expression of cell cycle, EMT, and metastasis related markers.
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- CS might pose a potential risk of ovarian cancer progression.
Cigarette
smoke (CS) contains over 60 well-established carcinogens, and there are
strong links between these carcinogens and smoking-induced cancers. In
this study we investigated whether three types of cigarette smoke
extracts (CSEs), 3R4F (standard cigarette), CSE1 and CSE2 (two
commercial cigarettes), affect the proliferation, migration, and
invasive activity of BG-1 human ovarian cancer cells. All three types of
CSEs increased BG-1 cell proliferation at nicotine concentrations of
1.5 μM–2.1 μM in a cell viability assay. The protein expressions of
cyclin D1 and cyclin E1 were increased, while p21 and p27 expression was
decreased by Western blot assay. However, they did not show a
consistent dose-dependent tendency. The protein expressions of Bax and
p53, pro-apoptotic genes, were also decreased by CSEs. The expression of
E-cadherin, an epithelial marker, was reduced in the treatment of CSEs
while the expression of its reverse transition marker, N-cadherin, was
slightly increased by CSEs containing 2.1 μM of nicotine, but a
statistical significance was not observed. Epithelial-mesenchymal
transition (EMT)-associated transcriptional factors, Snail and Slug,
were also up-regulated by treatment with CSEs, indicating that CSEs can
increase the EMT process in BG-1 ovarian cancer cells. In addition,
CSEs increased the migratory and invasive propensity of cancer cells.
These functional alterations were associated with changes in
metastasis-related gene expression. Upon exposure to CSEs, the
expression of MMP-9 and cathepsin D was increased. Taken together, we
confirmed that CSEs increased the growth, migration, and invasion of
human ovarian cancer cells by regulating cell cycle, apoptosis, EMT, and
metastasis related cellular markers and signaling proteins. Based on
the results, cigarette smokers of women might be at a higher risk of
ovarian cancer than non-smokers.
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