Regulatory Effect of E2,IL-6 and IL-8 on the Growth of Epithelial Ovarian Cancer Cells

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To determine the regulatory effects of estrogen and cytokine IL-6 and IL-8 on the growth of epithelial ovariancancer (OVCA),we first examined the status of estrogen receptors (ERα and ERβ),IL-6 receptor (IL-6Rα andgp130),and IL-8 receptor (IL-8RA and IL-8RB) on five epithelial OVCA cell lines by semiquantitative RT-PCRand Western blot analysis.Results showed that the expressions of these receptors were variable on the five cells.Those OVCA cells expressing the receptors were selected to study related molecular mechanism.MTT assay wasperformed to observe the effects of 17β-estradioi (E2),IL-6 and IL-8 on cell proliferation.We discovered that E2markedly promoted the proliferation of CAOV-3 and OVCAR-3 cell in a time- and dose-dependent manner.Tamoxifen (Txf),an ER inhibitor,completely blocked the proliferation of the E2-induced cells,and IL-6- or/andIL-8-neutralizing antibody only showed partially blocking activity.IL-6 and IL-8 were able to significantlystimulate CAOV-3 and OVCAR-3 cell proliferation in a time-and dose-dependent manner,which had a potentialsynergistic effect on CAOV-3 cells but not on OVCAR-3 cells.The cell proliferation induced by these two cytokineswas abolished completely by their specific neutralizing antibodies,partially by Txf,but not by unrelated goat IgC~Taken together,our results suggested that estrogen,IL-6 and IL-8 could modulate OVCA growth by forming areciprocal cascade with amplifying effect.Cellular & Molecular Immunology.2005;2(5):365-372. To determine the regulatory effects of estrogen and cytokine IL-6 and IL-8 on the growth of epithelial ovarian cancer (OVCA), we first examined the status of estrogen receptors (ERα and ERβ), IL-6 receptor (IL-6Rα and gp130) , and IL-8 receptor (IL-8RA and IL-8RB) on five epithelial OVCA cell lines by semiquantitative RT-PCR and Western blot analysis. Results showed that the expressions of these receptors were variable on the five cells. receptors were selected to study related molecular mechanism. MTT assay wasperformed to observe the effects of 17β-estradioi (E2), IL-6 and IL-8 on cell proliferation. We discovered that E2 highly promoted the proliferation of CAOV-3 and OVCAR-3 cell in a time- and dose-dependent manner. Tamoxifen (Txf), an ER inhibitor, completely blocked the proliferation of the E2-induced cells, and IL-6- or / and IL-8-neutralizing antibody only showed partially blocking activity. IL-6 and IL-8 were able to significantlystimulate CAOV-3 and OVCAR-3 cell proliferation in a time-and dose-dependent manner, which had a potentialsynergistic effect on CAOV-3 cells but not on OVCAR-3 cells. The cell proliferation induced by these two cytokines was abolished completely by their specific neutralizing antibodies, partially by Txf, but not by unrelated goat IgC ~ Taken together, our results suggest that estrogen, IL-6 and IL-8 could modulate OVCA growth by forming areciprocal cascade with amplifying effect. Cellular & Molecular Immunology. 2005; 2 (5): 365-372 .
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