Calcium homeostasis in cisplatin resistant epithelial ovarian cancer


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Kucukkaya B., BAŞOĞLU H., Erdag D., AKBAŞ F., SÜSGÜN S., Yalcintepe L.

General Physiology and Biophysics, vol.38, no.4, pp.353-363, 2019 (SCI-Expanded) identifier identifier

  • Publication Type: Article / Article
  • Volume: 38 Issue: 4
  • Publication Date: 2019
  • Doi Number: 10.4149/gpb_2019013
  • Journal Name: General Physiology and Biophysics
  • Journal Indexes: Science Citation Index Expanded (SCI-EXPANDED), Scopus
  • Page Numbers: pp.353-363
  • Keywords: Calcium, Cisplatin, Drug resistance, MDAH-2774
  • İstanbul Yeni Yüzyıl University Affiliated: Yes

Abstract

Intracellular calcium concentration ([Ca2+]i) may have an important role in the development of chemoresistance, which is an essential problem in cancer chemotherapy. Cisplatin (DDP), which modulates the intracellular calcium concentration by different mechanisms, is an antineo-plastic agent with high success rate in cancer therapies. We investigated the regulatory role of [Ca2+] in cisplatin resistance in epithelial ovarian cancer cell line, in MDAH-2774, and its chemoresistant subclone MDAH-2774/DDP. The measurement of [Ca2+]i using fluorescence microscope, and flow cytometry revealed that the amount of intracellular calcium decreased in cisplatin resistant cells compared to the amounts in parental cells. mRNA expression profiles of calcium homeostasis-associated major genes (IP3R1/2/3, RYR1/2, SERCA1/2/3, NCX1/2/3, PMCA1/2/3, and PMCA4) decreased in cisplatin resistant cell line in comparison to the expression profiles in parental cells. Owing to the changes in the expression of genes involved in calcium regulation, these results show, drug resistance may be prevented by introducing a new perspective on the use of inhibitors and activators of these genes, and thus of cytostatic treatment strategies, due to changes in the expression of genes involved in calcium regulation.