| Ovarian cancer(OC) and Breast cancer are hormone-associated turnors. Breast canceraccounts for 3l% in women tumors. OC is the third frequently diagnosed malignanttheors of gynecology and the leading cause of cancer death in woman. Ovmp not orilycould secret some sex hormones, such as estrogen, progesterone, androgen andglucocorticoids (GCs), but also is a target organ for steroid hormones. In recent years,some stUdies suggest, just like breast cancer and prostate cancef, steroid hormones mightplay an importan role in the proliferation and differentiation of ovarian cancer.As steroid hormones, GCs exert profound effects on the proliferation anddifferentiation of many types of normaI and malignant ceIIs, such as fibrobIasts andlymphatic leukemia cells. However, uP to noW there are few reports aboot the effects ofGCs on biological behaviors of ovarian cancer and breast cancer. Therefore, it isnecessary to fiJrther explore the influence of GCs on ovedan cancer. breast cancer andtheir underlying mechanisms.To stUdy the effects of glucocorticoids on 3AO(a human ovarian carcinoma cell line),MCF-7(a human breast cancer cell line), cells were treated with same concentrations ofdexaxnethasone(Dex), estrogen, progesterone, androgen(l0-'moim), for up to five days. Itwas found repeatedly that the proliferation of 3AO. MCF-7 cells was markedly inhibitedby Dex. Sex steroid hormones had little effects on the proliferation of 3AO cells. AKPactivity increased significantly after tredrient with Dex in 3AO. MCF-7 cells and had noeffects with sex steroid hormones in 3AO cells. Furthermore, Dex and sex steroidhormones could suppress the expression of CA125 turnor maker in 3AO cells. So, Dexcould inhibit the proliferation of 3AO. MCF-7, cells, but sex steroid hormones had noeffects on the proliferation of 3AO cells.When 3AO. MCF-7 cells were treated with Dex in combination with RU486, aspecific glucocorticoid receptor (GR) anagonist, induction of AKP activity by Dex wascompletely bluned. These results suggested that the cellular effects of Dex on 3AO.MCF-7 cells might be conveyed through the intracelluar ligand-activated transcriptionalregulatory protein termed GR. Prompted by this proposal, GR expression in 3AO'MCF-7 cells was further stUdied at protein levels with the standard radioligand bindingassay. Binding stUdies showed that there existed a saturable, high-affinity GR in 3AO.MCF-7 cells, with a maximum binding caPacity (Bmax) of 92.26t23.30 fmol/l0' cells.62.l8fl3.64 fmol/l0' ceIls, and a constant dissociation(Kd) value of l.37f0.l9tunoW. l .77i0. l2 nmol/L, respectively The results of this pat clearly demonstrated thatthere was fimctional GR in 3AO and MCF-7 cells and the cellular effectS of Dex weremediated by GR. Since GR is the key factor in the signal transduction of glucocorticoidaction, it should be of interest to study the homologous regulation of GR in 3AO andMCF-7 cells. It was shown that the GR binding activity in 3AO and MCF-7 cells could besignificanly down-regUlated by Dex in a time- and dose-dependent manner.By fiow cytometry(FCM) analysis, it was shown that Dex could induce a recruitmentof cells in the GJG, phase with a reduction of cells in S phase. The expression ofp21/WAF1 in 3AO cells was analyzed by Westem Blot. It was found that the p2l/WAFllevels were increased significantly and rapidly by Dex in a dose- and time-dependent manner, and this effect could be reversed completely by the GR antagonist, Ru486, suggesting p21/WAFl might be involved in Dex-mediated inhibition of SAO cells proliferation. Meantime, Dex could inhibit MCF-7 cell cycle progression in the 0,/G, phase, the expression of p21 had little changes.It is known that intracellular transmission of many extracellular signals is mediated by mitogen-activated protein kinase(MAPK) cascades. Using the antibodies against the phosphorylated forms of the MAP kinases, we tested the effects of Dex on the activity of the ERK1/2 in...
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