Mirzaei Zahra, Zarei Sadegh, Sayadi Ahmadreza, Hosseiniara Reza, Karimabad Mojgan Noroozi, Mahmoodi Mehdi
Department of Clinical Biochemistry, Afzalipour Faculty of Medicine, Kerman University of Medical Sciences, Kerman, Iran.
Department of Clinical Biochemistry, School of Medicine, Rafsanjan University of Medical Sciences, Rafsanjan, Iran.
BMC Complement Med Ther. 2025 Jan 22;25(1):15. doi: 10.1186/s12906-024-04716-7.
This study aimed to investigate the synergistic effects of the chemotherapy drug Carfilzomib (CFZ) and Pistachio hull extract on the SK-BR3 breast cancer cell line.
In this experimental study, we evaluated the effect of Pistachio hull extract and CFZ as standalone treatments on cell viability using the MTT assay at 24- and 48-hours post-treatment. Following this, we conducted combination therapy analyses to assess the potential synergistic relationship between Pistachio hull extract and CFZ after 24- and 48-hours of treatment on both the SK-BR3 breast cancer cell line and the MCF10A normal cell line. We utilized real-time PCR to measure the expression levels of MDR1, MRP1, NF-κB p65, and Caspase3 genes. Additionally, the NF-κB p65 transcription factor was evaluated using ELISA after 24- and 48-hours.
The MTT assay revealed IC50 values of 2.014 mg/mL and 1.031 mg/mL in the SK-BR3 cell line, and 3.265 mg/mL and 2.994 mg/mL in the MCF10A cell line at 24- and 48-hours post-treatment with Pistachio hull extract. CFZ concentrations of 0.181 × 10 mg/mL and 0.0057 × 10 mg/mL in the SK-BR3 cell line, as well as 5.54 × 10 mg/mL and 2.51 × 10 mg/mL in the MCF10A cell line, inhibited growth by up to 50%. The analysis of combination therapy indicated a synergistic effect between the two treatments after both 24- and 48-hours of exposure. Real-time PCR results demonstrated significant alterations in the expression of MDR1, MRP1, NF-κB p65, and Caspase3 genes, along with changes in NF-κB p65 protein levels in both cell lines following treatment with Pistachio hull extract, CFZ, or their combination compared to the control group (p < 0.05).
The findings highlight the effectiveness of CFZ as a proteasome inhibitor when used in conjunction with Pistachio hull extract in breast cancer cell lines. Therefore, both CFZ and Pistachio hull extract, whether administered alone or in combination, represent promising molecular targets for breast cancer treatment.
本研究旨在探讨化疗药物卡非佐米（CFZ）与开心果壳提取物对SK-BR3乳腺癌细胞系的协同作用。
在本实验研究中，我们在处理后24小时和48小时使用MTT法评估开心果壳提取物和CFZ单独处理对细胞活力的影响。在此之后，我们进行联合治疗分析，以评估在对SK-BR3乳腺癌细胞系和MCF10A正常细胞系进行24小时和48小时处理后，开心果壳提取物和CFZ之间潜在的协同关系。我们利用实时荧光定量PCR来测量多药耐药蛋白1（MDR1）、多药耐药相关蛋白1（MRP1）、核因子κB p65（NF-κB p65）和半胱天冬酶3（Caspase3）基因的表达水平。此外，在24小时和48小时后使用酶联免疫吸附测定法评估NF-κB p65转录因子。
MTT法显示，在处理后24小时和48小时，开心果壳提取物处理的SK-BR3细胞系的半数抑制浓度（IC50）值分别为2.014 mg/mL和1.031 mg/mL，MCF10A细胞系的IC50值分别为3.265 mg/mL和2.994 mg/mL。SK-BR3细胞系中CFZ浓度为0.181×10 mg/mL和0.0057×10 mg/mL，以及MCF10A细胞系中CFZ浓度为5.54×10 mg/mL和2.51×10 mg/mL时，生长抑制率高达50%。联合治疗分析表明，两种处理在暴露24小时和48小时后均具有协同作用。实时荧光定量PCR结果表明，与对照组相比，在用开心果壳提取物、CFZ或它们的组合处理后，两种细胞系中MDR1、MRP1、NF-κB p65和Caspase3基因的表达有显著变化，同时NF-κB p65蛋白水平也有变化（p < 0.05）。
研究结果突出了CFZ作为蛋白酶体抑制剂与开心果壳提取物联合用于乳腺癌细胞系时的有效性。因此，CFZ和开心果壳提取物，无论是单独使用还是联合使用，都是乳腺癌治疗有前景的分子靶点。
