Home Bratislava Medical Journal 2019 Bratislava Medical Journal Vol.120, No.6, p.468–475, 2019

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Published Monthly, in English
Founded: 1919
ISSN 0006-9248
(E)ISSN 1336-0345

Impact factor 1.2

 

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Bratislava Medical Journal Vol.120, No.6, p.468–475, 2019

Title: Effects of carfilzomib alone and in combination with cisplatin on the cell death in cisplatin-sensitive and cisplatin-resistant ovarian carcinoma cell lines
Author: S. Zarei, J. Zavar Reza, H. Zarei Jaliani, M. R. Hajizadeh, S. Sargazi, H. Hosseinian

Abstract: BACKGROUND: Previous studies on the efficacy of platinum-based drugs and selective inhibitors of proteasome have revealed promising outcomes. This study is aimed to evaluate the effects of the combination of cisplatin and carfilzomib on the cell death induction and drug efflux transporters expression in cisplatin-sensitive (A2780s) and cisplatin-resistant (A2780cp) ovarian cancer cells lines.
METHODS: MTT cytotoxic assay was conducted to determine the cytotoxicity. Drug interactions were analyzed based on Chou-Talalay’s principles and real-time PCR analysis was performed to determine possible alterations in mRNA levels of MRP1 and BCRP.
RESULTS: A2780s cells were more susceptible to both cisplatin and carfilzomib while analyses of drug interactions between the two agents showed synergistic effects in all affected fractions of drug-treated A2780s and A2780cp cells (CI<0.9) with the combination indices being significantly lower in A2780cp cells (p < 0.01). We also found that although mRNA levels of BCRP and MRP1 were significantly altered in both cells exposed to each drug alone, only the combination regimen was able to significantly reduce the mRNA levels of these genes in A2780cp cells (p<0.001).
CONCLUSION: This combination might be a potential strategy for suppressing cell growth via downregulating the drug efflux transporters expression, especially in cisplatin-resistant ovarian cancer cells (Fig. 3, Ref. 45).

Keywords: cisplatin, carfilzomib, drug combination, ovarian neoplasms
Published online: 21-Jun-2019
Year: 2019, Volume: 120, Issue: 6 Page From: 468, Page To: 475
doi:10.4149/BLL_2019_075


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