Corticosteroids induce chemotherapy resistance in the majority of tumour cells from bone, brain, breast, cervix, melanoma and neuroblastoma

Zhang, Chengwen; Beckermann, Benjamin M.; Kallifatidis, Georgios; Liu, Zheng; Rittgen, Werner; Edler, Lutz; Büchler, Peter; Debatin, Klaus Michael; Büchler, Markus W.; Friess, Helmut; Herr, Ingrid

doi:10.3892/ijo.29.5.1295

Cited by 59 publications

(60 citation statements)

References 16 publications

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“…To our knowledge, the present in vitro study was the first to address this question, and it is reassuring that our results showed, in the majority of dexamethasone drug concentrations and time-points studied, no inhibition of the cytotoxic activity of cetuximab suggesting no evidence for an adverse interaction between cetuximab and dexamethasone in head and neck cancer cell lines. So these findings are partially in contrast to those reported by Zhang et al (19) who demonstrated glucocorticoid-induced resistance to chemotherapy in the majority of cell lines derived from various malignancies including brain, breast, cervix, melanoma and neuroblastoma. Gassler et al (14) found an anti-apoptotic effect of glucocorticoids in tissue samples from lung cancer.…”

Section: Discussioncontrasting

confidence: 56%

Does dexamethasone inhibit anticancer activity of cetuximab in squamous cell carcinoma cell lines of the head and neck?

Wagenblast

Baghi²,

Mörtel³

et al. 2009

Oncol Rep

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Abstract. Glucocorticoids such as dexamethasone are widely used as comedication in the treatment of head and neck cancer, e.g., to improve appetite and decrease weight loss and fatigue in patients with advanced disease or as antiallergic and antiemetic prophylaxis during anti-EGFR therapy. However, the literature suggests that dexamethasone induces resistance to antineoplastic agents in many solid tumor models in vitro and in vivo. Since this phenomenon has never been investigated in head and neck cancer, the present study was conducted to investigate the effect of dexamethasone on the antiproliferative activity of cetuximab in vitro in squamous cell carcinoma of the head and neck (SCCHN) cell lines. The antiproliferative effect of the anti-EGFR agent cetuximab alone and in combination with increasing concentrations of dexamethasone was examined in eight SCCHN cell lines at three different time-points (24, 48 and 72 h). Cell growth inhibition and viability were measured quantitatively using WST and LDH assays. Absolute tumor cell numbers were determined by cell counting in a Rosenthal chamber. Cetuximab alone inhibited the growth of all eight SCCHN cell lines significantly (p=0.008). In some cases the addition of dexamethasone reduced the antiproliferative activity of cetuximab (p≤0.038) but remained significant in all of the eight SCCHN cell lines compared with untreated controls (p≤0.028) at each drug concentration and each time-point. In contrast to the results reported for other tumor models, in our study dexamethasone showed in the majority of the evaluated dexamethasone drug concentrations and timepoints no inhibition of the cytotoxic activity of cetuximab. The reasons for these discrepant findings are unclear but may be related to the degree of tumor cell differentiation or proliferation rate. Thus, further studies are required to elucidate the molecular mechanisms underlying the interaction between dexamethasone and cetuximab in different tumors.

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Section: Discussioncontrasting

confidence: 56%

Does dexamethasone inhibit anticancer activity of cetuximab in squamous cell carcinoma cell lines of the head and neck?

Wagenblast

Baghi²,

Mörtel³

et al. 2009

Oncol Rep

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“…2). Additionally, CDDP and 5-FU induced apoptosis, whereas the inhibition of apoptosis by DEX promoted proliferation in various established and primary cancer cells (12). The enhanced secretion of Cys C induced by co-treatment with DEX might be correlated with the inhibition of apoptosis as well as the abovementioned transcriptional regulation.…”

Section: Discussionmentioning

confidence: 96%

Effect of dexamethasone on extracellular secretion of cystatin C in cancer cell lines

et al. 2012

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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. IntroductionCystatin C (Cys C) is a non-glycosylated cationic 13.3-kDa protein belonging to the cystatin superfamily of cysteine protease inhibitors (1-3). Cys C is produced by nucleated cells and is secreted into the blood at a constant rate (1-3). It is freely filtered through the glomerular membrane, completely re-absorbed and then catabolized in the proximal tubular cells (1-3). Thus, similarly to creatinine, the biological fate of Cys C is a good endogenous marker of the glomerular filtration rate (GFR).In patients with esophageal cancer, cisplatin (CDDP) is used as a neoadjuvant or as a post-operative adjuvant chemotherapy in combination with continuous infusion of 5-fluorouracil (5-FU) (4,5). When CDDP-based chemotherapy is administered, antiemetic drugs, such as dexamethasone (DEX), 5-HT 3 serotonin receptor antagonists or aprepitant are administered to prevent treatment-associated nausea and vomiting (6). A transient elevation was previously reported in serum Cys C concentration during the perioperative chemotherapy period in patients with esophageal cancer. We suggested that renal function estimates determined on the basis of serum Cys C levels during this treatment period might be misleading (7).To understand the effect of DEX and other drugs in detail, it is crucial to investigate the renal effects associated with serum Cys C concentration. The aim of this study was to investigate the ability of DEX to induce Cys C secretion in human cancer cell lines, as well as the effect of CDDP, 5-FU and mifepristone (RU-486) on Cys C secretion. Materials and metho...

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“…[7][8][9][10][11][12][13] There have been conflicting results concerning the antitumor effects of GCs. In some tumors, GCs assist tumor progression by inhibiting chemotherapy-induced or immunoresponse-induced apoptosis, promoting tumor growth 24 and increasing cancer invasiveness. [25][26][27] Conversely, GC induces tumor apoptosis by negatively affecting the transcription of nuclear factor kappaB (NF-jB ), an important regulator of the immune system and antiapoptotic mechanisms, in various cell lines and lymphocytes.…”

Section: Discussionmentioning

confidence: 99%

Steroid receptor expression in thymomas and thymic carcinomas

Mimae

Tsuta

Takahashi

et al. 2011

Cancer

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BACKGROUND: Although protein expressions of glucocorticoid receptor (GR), estrogen receptors (ERa and ERb), progesterone receptor A (PgR-A), and androgen receptor (AR) were shown to play roles in the growth and differentiation of normal thymus and thymic tumors, to the authors' knowledge their association with patient characteristics and prognosis has yet to be determined. METHODS: A series of 140 thymic epithelial tumors (57 type A þ AB thymomas, 40 type B1 þ B2 thymomas, 6 type B3 thymomas, and 37 thymic carcinomas) were examined for GR, ERa, ERb, PgR-A, and AR expression using immunohistochemistry. In addition, the correlation between expression of these hormone receptors and clinicopathologic factors and overall survival (OS) was assessed. RESULTS: GR and ERb demonstrated a high rate of expression in thymomas and thymic carcinomas (82.9% and 76.4%, respectively), whereas rates of ERa, PgR-A, and AR expression were low (13.6%, 0.71%, and 23.6%, respectively). A significant correlation (P < .05) was found between ERa expression and tumor size and between ERb expression and tumor stage. Multivariate analyses revealed that histologic subtype (P ¼ .0039), tumor stage (P ¼ .0012), and GR expression (P ¼ .0025) were significantly correlated with the 10-year OS rate. CONCLUSIONS: GR and ERb demonstrated high rates of expression in thymomas and thymic carcinomas. Furthermore, multivariate analysis revealed that GR expression was associated with better prognosis in patients with surgically resected thymomas and thymic carcinomas. Cancer 2011;117:4396-

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Corticosteroids induce chemotherapy resistance in the majority of tumour cells from bone, brain, breast, cervix, melanoma and neuroblastoma

Cited by 59 publications

References 16 publications

Does dexamethasone inhibit anticancer activity of cetuximab in squamous cell carcinoma cell lines of the head and neck?

Does dexamethasone inhibit anticancer activity of cetuximab in squamous cell carcinoma cell lines of the head and neck?

Effect of dexamethasone on extracellular secretion of cystatin C in cancer cell lines

Steroid receptor expression in thymomas and thymic carcinomas

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