Sharma Girish, Singh Rana P, Chan Daniel C, Agarwal Rajesh
Department of Pharmaceutical Sciences, School of Pharmacy, University of Colorado Health Sciences Center, 4200 East 9th Avenue, Box C238, Denver, CO 80262, USA.
Anticancer Res. 2003 May-Jun;23(3B):2649-55.
The high systemic toxicity of chemotherapeutic agents limits their use to treat clinical lung cancer. These limitations could be minimized/overcome by using non-toxic phytochemicals, like, silibinin.
We used small cell lung carcinoma cells (SCLC) SHP-77 and non-small cell lung carcinoma cells (NSCLC) A-549, analyzing cell growth inhibition and death with Trypan blue exclusion, indices of the cell cycle progression with flow cytometry and apoptosis with propidium iodide and Hoechst 33342.
Silibinin (25, 50 and 100 microM) treatment of SHP-77 and A-549 cells resulted in their growth inhibition and cell death. Cell cycle studies showed a small increase in G0-G1 population at all the time intervals in SHP-77 cells, however, in A-549 cells, a slight increase in G0-G1 but strong increase in S-phases was observed at lower treatment times, and a strong increase in G0-G1 population at 72 hours. Quantitative apoptotic studies showed that silibinin causes apoptotic cell death in both a dose- and a time-dependent manner with SHP-77 cells showing more apoptotic effect than A-549 cells.
Silibinin significantly induces growth inhibition, a moderate cell cycle arrest and a strong apoptotic death in both small cell and non-small cell human lung carcinoma cells, which warrants further studies to assess the efficacy of this non-toxic agent in animal lung tumor models.
化疗药物的高全身毒性限制了其在临床肺癌治疗中的应用。使用无毒的植物化学物质,如水飞蓟宾,可将这些限制最小化/克服。
我们使用小细胞肺癌细胞(SCLC)SHP-77和非小细胞肺癌细胞(NSCLC)A-549,通过台盼蓝排斥法分析细胞生长抑制和死亡情况,通过流式细胞术分析细胞周期进程指标,并用碘化丙啶和Hoechst 33342分析细胞凋亡情况。
水飞蓟宾(25、50和100微摩尔)处理SHP-77和A-549细胞导致其生长抑制和细胞死亡。细胞周期研究表明,SHP-77细胞在所有时间间隔内G0-G1期细胞群体略有增加,然而,在A-549细胞中,在较低处理时间观察到G0-G1期略有增加但S期显著增加,在72小时时G0-G1期细胞群体显著增加。定量凋亡研究表明,水飞蓟宾以剂量和时间依赖性方式导致凋亡细胞死亡,SHP-77细胞的凋亡效应比A-549细胞更明显。
水飞蓟宾在人小细胞和非小细胞肺癌细胞中均显著诱导生长抑制、中度细胞周期阻滞和强烈的凋亡死亡,这值得进一步研究以评估这种无毒药物在动物肺癌模型中的疗效。