Chavoshi Hadi, Vahedian Vahid, Saghaei Somaiyeh, Pirouzpanah Mohammad Bagher, Raeisi Mortaza, Samadi Nasser
Hematology and Oncology Research Center, Tabriz University of Medical Sciences, Tabriz, Iran. Email:
Asian Pac J Cancer Prev. 2017 Aug 27;18(8):2243-2247. doi: 10.22034/APJCP.2017.18.8.2243.
Herbal-derived medicines have introduced as sources of novel drugs due to minimum systemic side effects. Silibinin as a flavonoid compound has showed with effective chemotherapeutic effects on different cancers. Here, we investigated the impact of combination therapy of silibinin, with paclitaxel and cisplatin in inhibition of proliferation and induction of apoptosis in MCF-7 cells. Cell proliferation was assessed by MTT assay and the percentage of apoptotic cells was measured using flowcytometric assay. Understand of molecular mechanism of this combination related to apoptotic pathway were evaluated by Real Time RT-PCR assays. The IC50 values for silibinin, paclitaxel and cisplatin were 160 ± 22.2 μM, 33.7 ± 4.2 nM and 3.2 ± 0.5 μM, respectively. Paclitaxel and cisplatin induced higher percentage of apoptosis in MCF-7 (P < 0.05). Treatment of cell line with combination of silibinin and paclitaxel or cisplatin showed enhanced early apoptosis 56% and 61%, respectively (P < 0.05). Gene expression patterns demonstrated a significant decrease in anti-apoptotic Bcl-2 with increase in pro-apoptotic Bax, P53, BRCA1 and ATM mRNA levels. Taken together combination therapy of breast cancer cells by applying paclitaxel or cisplatin with silibinin synergistically increases the anti-proliferative effect of single agents.
由于全身副作用最小,草药衍生药物已作为新型药物来源被引入。水飞蓟宾作为一种黄酮类化合物,已显示出对不同癌症具有有效的化疗作用。在此,我们研究了水飞蓟宾与紫杉醇和顺铂联合治疗对MCF-7细胞增殖抑制和凋亡诱导的影响。通过MTT法评估细胞增殖,并使用流式细胞术测定凋亡细胞的百分比。通过实时RT-PCR分析评估这种联合治疗与凋亡途径相关的分子机制。水飞蓟宾、紫杉醇和顺铂的IC50值分别为160±22.2μM、33.7±4.2 nM和3.2±0.5μM。紫杉醇和顺铂诱导MCF-7细胞凋亡的百分比更高(P<0.05)。用水飞蓟宾与紫杉醇或顺铂联合处理细胞系分别显示早期凋亡增加56%和61%(P<0.05)。基因表达模式显示抗凋亡Bcl-2显著降低,同时促凋亡Bax、P53、BRCA1和ATM mRNA水平升高。综上所述,紫杉醇或顺铂与水飞蓟宾联合治疗乳腺癌细胞可协同增强单一药物的抗增殖作用。