Zhou Liguang, Liu Peishu, Chen Bo, Wang Yu, Wang Xuping, Chiriva Internati Maurizio, Wachtel Mitchell S, Frezza Eldo E
Departments of Obstetrics and Gynecology, Qilu Hospital of Shandong University, 250012 Jinan, ROC.
Anticancer Res. 2008 Mar-Apr;28(2A):1119-27.
Drug resistance and tumor metastasis are the main causes of treatment failure and mortality in cancer patients. Silibinin, a naturally occurring flavanone, has been shown to be a potent sensitizer for apoptosis induced by a variety of anticancer drugs. In this study, whether silibinin could overcome chemoresistance and reduce the invasiveness of A2780/taxol cells was investigated.
A2780 and A2780/taxol cells were treated with silibinin alone and in combination with paclitaxel. Cell viability was determined by MTT assay while apoptosis and cell cycle progression were assessed by flow cytometric analysis. Matrigel invasion assays assessed the invasive activity. Protein and mRNA levels influenced by the treatment were studied by Western blots and quantitative real-time PCR.
Silibinin enhanced the sensitivity of A2780/taxol cells to paclitaxel, increased paclitaxel-induced apoptosis and G2/M arrest consistent with the down-regulation of survivin and P-glycoproteins. A2780/taxol cells demonstrated a two-fold increase in invasiveness ability compared to A2780 cells, whereas the invasive potential was reduced dramatically by silibinin.
These results suggest silibinin in combination with paclitaxel may be a beneficial chemotherapeutic strategy, especially in patients with tumors refractory to paclitaxel alone.
耐药性和肿瘤转移是癌症患者治疗失败和死亡的主要原因。水飞蓟宾是一种天然存在的黄酮类化合物，已被证明是多种抗癌药物诱导凋亡的有效增敏剂。在本研究中，研究了水飞蓟宾是否能克服化疗耐药性并降低A2780/紫杉醇细胞的侵袭性。
单独用水飞蓟宾以及将其与紫杉醇联合处理A2780和A2780/紫杉醇细胞。通过MTT法测定细胞活力，同时通过流式细胞术分析评估细胞凋亡和细胞周期进程。基质胶侵袭试验评估侵袭活性。通过蛋白质印迹和定量实时PCR研究受处理影响的蛋白质和mRNA水平。
水飞蓟宾增强了A2780/紫杉醇细胞对紫杉醇的敏感性，增加了紫杉醇诱导的细胞凋亡和G2/M期阻滞，这与生存素和P-糖蛋白的下调一致。与A2780细胞相比，A2780/紫杉醇细胞的侵袭能力增加了两倍，而水飞蓟宾显著降低了其侵袭潜力。
这些结果表明，水飞蓟宾与紫杉醇联合使用可能是一种有益的化疗策略，特别是对于单独使用紫杉醇难治的肿瘤患者。
