title: Effect of dexamethasone on extracellular secretion of cystatin C in cancer cell lines.
abstract: The aim of the present study was to investigate dexamethasone (DEX)-induced secretion of cystatin C (Cys C) and the effect of cisplatin (CDDP) and 5-fluorouracil (5-FU) on Cys C secretion in human cancer cell lines. KYSE150, A549 and Caki-2 human cancer cell lines were cultured on plastic dishes and treated with DEX (100 nM) for 24, 48 and 72 h. KYSE150 cells were co-treated with DEX, CDDP (10 μM), and 5-FU (2 μM). The effects of DEX, CDDP and 5-FU on cell viability were evaluated. Results showed Cys C secretion levels in the culture medium of DEX-treated KYSE150 cells to be 1.8- to 2.3-fold higher compared to those in the culture medium of control cells. A similar tendency was observed in A549 cells at all the time points, whereas a significant increase in the Cys C secretion by Caki-2 cells was observed only 24 h after DEX treatment. Regarding KYSE150 cells, the secretion of Cys C was also enhanced by co-treatment of CDDP or 5-FU with DEX, although it was not affected by the co-administration of DEX and mifepristone, a glucocorticoid receptor antagonist. At concentrations that are typically used in esophageal cancer chemotherapy, CDDP and 5-FU demonstrated a moderate level of cytotoxicity in KYSE150 cells in contrast to DEX. These findings suggested that DEX has the potential to enhance the extracellular secretion of Cys C in esophageal cancer cells, possibly due to the transcriptional regulation mediated by glucocorticoid receptor activity.
authors.affiliation: Department of Pharmaceutical Health Care, Faculty of Pharmaceutical Sciences, Himeji Dokkyo University, Himeji, Hyogo 670-8524;
authors.forename: Chika
authors.initials: C
authors.lastname: Yamawaki
authors.affiliation: Department of Pharmaceutical Health Care, Faculty of Pharmaceutical Sciences, Himeji Dokkyo University, Himeji, Hyogo 670-8524;
authors.forename: Minoru
authors.initials: M
authors.lastname: Takahashi
authors.affiliation: Department of Pharmaceutical Health Care, Faculty of Pharmaceutical Sciences, Himeji Dokkyo University, Himeji, Hyogo 670-8524;
authors.forename: Kohji
authors.initials: K
authors.lastname: Takara
authors.affiliation: Department of Pharmacy, Kobe University Hospital, Kobe, Hyogo 650-0017;
authors.forename: Manabu
authors.initials: M
authors.lastname: Kume
authors.affiliation: Department of Pharmacy, Kobe University Hospital, Kobe, Hyogo 650-0017;
authors.forename: Midori
authors.initials: M
authors.lastname: Hirai
authors.affiliation: Department of Analytical and Bioinorganic Chemistry, Kyoto Pharmaceutical University, Kyoto 607-8414, Japan.
authors.forename: Hiroyuki
authors.initials: H
authors.lastname: Yasui
authors.affiliation: Department of Pharmaceutical Health Care, Faculty of Pharmaceutical Sciences, Himeji Dokkyo University, Himeji, Hyogo 670-8524;
authors.forename: Tsutomu
authors.initials: T
authors.lastname: Nakamura
keywords: 5-fluorouracil; cisplatin; cystatin C; dexamethasone; esophageal cancer; glucocorticoid receptor