Department of Biochemistry, Faculty of Medicine, Shahid Beheshti University of Medical Sciences, Tehran, Iran
Department of Biochemistry, Faculty of Medicine, Iran University of Medical Sciences, Tehran, Iran
Anticancer Agents Med Chem. 2020;20(18):2285-2292. doi: 10.2174/1871520620666200807103903.
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.
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.
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.
Overexpression of MDR1 as well as a marked 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.
Our results indicated that FMSP may be considered as a promising therapeutic agent for the prevention and management of chemoresistance in breast cancer cells.
乳腺癌是全球女性中最常见的癌症类型。尽管近年来癌症治疗取得了重大进展，但癌细胞通常会发展出逃避化疗诱导细胞死亡的机制。因此，需要新的策略来逆转癌症的化疗耐药性。
本研究旨在探讨一种新合成的二茂铁衍生物 1-二茂铁基-3-(4-甲基磺酰基苯基)丙烯-1-酮（FMSP）对 MCF-7 细胞顺铂耐药性的影响，重点研究其对多药耐药-1（MDR-1）和炎症相关 STAT3 通路的抑制作用。
构建顺铂耐药 MCF-7 细胞系，通过 MTT 法检测顺铂和 FMSP 对细胞活力的影响。采用 RT-PCR 和 Western blot 分析评估 MDR-1 的基因和蛋白表达以及 JAK2 和 STAT3 的磷酸化水平。
在顺铂耐药 MCF-7（MCF-7R）细胞中观察到 MDR1 的过度表达以及磷酸化 STAT3 水平的显著增加。FMSP 成功降低了 MCF-7R 细胞活力，并通过逆转 MDR1 表达和 STAT3 磷酸化状态，恢复了 MCF-7R 细胞对顺铂治疗的敏感性。
我们的研究结果表明，FMSP 可被视为预防和管理乳腺癌细胞化疗耐药性的有前途的治疗剂。
