Survivin, a member of apoptosis protein inhibitor family, is upregulated in various malignancies, especially in chemotherapy- and/or radiation-resistant cell lines. In this study, the correlation between the level of survivin expression and degree of apoptosis was investigated in three ovarian cancer lines (two chemoresistant cell lines SKOV-3 and OVCAR-3, as well as one chemosensitive cell line OV2008) treated with 5 microg/ml of cisdiamminedichloroplatinum (cisplatin, CDDP) for 24 h, 2 Gy of (60)Co irradiation, or 5 microg/ml CDDP for 3 h plus 2 Gy of (60)Co, respectively. We also evaluated the survivin mRNA abundance in patients with advanced ovarian cancers during CDDP treatment. In the ovarian cancer cell lines, survivin mRNA abundance and protein contents were significantly increased after the treatments while the apoptotic rates did not change in SKOV-3 and OVCAR-3. Moreover, in OVA2008 cells the expression of survivin decreased and the apoptotic rate significantly increased after CDDP and combined treatments. Survivin mRNA was not detectable in normal ovarian tissues and benign ovarian tumors. However, it was observed in the resected tumor specimens from 20 patients with advanced ovarian cancer. These results suggested that survivin may play an important role in the resistance to chemotherapy and radiotherapy in ovarian cancer cell lines and in the progression of ovarian tumors. Survivin may also provide a pivotal prognostic implication for epithelial ovarian carcinomas.
Recent studies showed that interleukin-8 (IL-8) played an important role in retinal neovascularization. In this study, the effects of genistein on the expression of IL-8 in the arising retinal pigment epithelia-19 cells were studied. The levels of IL-8 protein expression in supernatants were punctually detected by ELISA. When the cells were treated with hypoxia (5% CO2, 95% N2), IL-8 secretion increased from 0.29 +/- 0.04 to 2.59 +/- 0.42 ng/ml. To study calcium-dependent IL-8 expression, cells were treated with KCl at 25 mM, norepinephrine (NE) at 10 nM, and glutamate (Glu) at 1 microM for 8 h. As a result, the levels of IL-8 protein in supernatants were significantly increased compared with that in the controls. When the cells are treated with genistein (50, 100, 200 microM) for 30 min before hypoxia or stimulations by KCl, NE, and Glu, the elevated expression of IL-8 protein was all suppressed in a concentration-dependent manner. These results suggested that suppression of IL-8 expression in retinal pigment epithelial cells might partly account for the inhibitive effect of genistein on retinal neovascularization.
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