A Ferrocene Derivative Reduces Cisplatin Resistance in Breast Cancer Cells Through Suppression of MDR-1 Expression and Modulation of JAK2/STAT3 Signaling Pathway.
Anticancer Agents Med Chem. 2020 Aug 06;:
Authors: Noori S, Nourbakhsh M, Farzaneh S, Zarghi A
BACKGROUND: Breast cancer is the most common kind of cancer among women in the world. Despite major cancer therapy successes in recent years, cancer cells usually develop mechanisms to survive chemotherapy-induced cell death. Therefore, new strategies are needed to reverse cancer chemoresistance.
OBJECTIVE: The aim of this study was to investigate the effect of a recently-synthesized ferrocene derivative named 1- ferrocenyl-3-(4-methylsulfonylphenyl)propen-1-one (FMSP) on cisplatin resistance in MCF-7 cells, focusing on its inhibitory effects on multi-drug resistance-1 (MDR-1) and inflammatory-related STAT3 pathway.
METHODS: Cisplatin-resistant MCF-7 cells were developed and the effect of cisplatin and FMSP on cell viability was examined by MTT assay. RT-PCR and Western blotting analyses were performed to assess the gene and protein expression of MDR-1 as well as phosphorylation of JAK2 and STAT3.
RESULTS: Overexpression of MDR1 as well as a markedly increase in the level of phosphorylated STAT3 was observed in cisplatin-resistant MCF-7 (MCF-7R) cells. FMSP successfully reduced the MCF-7R cell viability and reversed both MDR1 expression and STAT3 phosphorylation status through which sensitivity of MCF-7R cells to cisplatin treatment was regained.
CONCLUSION: Our results indicated that FMSP may be considered as a promising therapeutic agent for the prevention and management of chemoresistance in breast cancer cells.
PMID: 32767949 [PubMed - as supplied by publisher]