Yamawaki Chika, Takahashi Minoru, Takara Kohji, Kume Manabu, Hirai Midori, Yasui Hiroyuki, Nakamura Tsutomu
Department of Pharmaceutical Health Care, Faculty of Pharmaceutical Sciences, Himeji Dokkyo University, Himeji, Hyogo 670-8524;
Department of Pharmacy, Kobe University Hospital, Kobe, Hyogo 650-0017;
Biomed Rep. 2013 Jan;1(1):115-118. doi: 10.3892/br.2012.21. Epub 2012 Oct 15.
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.
本研究的目的是调查地塞米松（DEX）诱导的胱抑素C（Cys C）分泌以及顺铂（CDDP）和5-氟尿嘧啶（5-FU）对人癌细胞系中Cys C分泌的影响。将KYSE150、A549和Caki-2人癌细胞系培养在塑料培养皿上，并用DEX（100 nM）处理24、48和72小时。将KYSE150细胞与DEX、CDDP（10 μM）和5-FU（2 μM）共同处理。评估DEX、CDDP和5-FU对细胞活力的影响。结果显示，与对照细胞培养基中的水平相比，DEX处理的KYSE150细胞培养基中的Cys C分泌水平高1.8至2.3倍。在所有时间点的A549细胞中均观察到类似趋势，而Caki-2细胞仅在DEX处理24小时后Cys C分泌显著增加。关于KYSE150细胞，CDDP或5-FU与DEX共同处理也增强了Cys C的分泌，尽管它不受DEX与糖皮质激素受体拮抗剂米非司酮共同给药的影响。与DEX相比，在食管癌化疗中通常使用的浓度下，CDDP和5-FU在KYSE150细胞中表现出中等水平的细胞毒性。这些发现表明，DEX有可能增强食管癌细胞中Cys C的细胞外分泌，这可能是由于糖皮质激素受体活性介导的转录调控。
