Rogalska Aneta, Marczak Agnieszka
Department of Thermobiology, Institute of Biophysics, Faculty of Biology and Environmental Protection, University of Lodz, Pomorska, Lodz, Poland E-mail :
Asian Pac J Cancer Prev. 2015;16(15):6535-9. doi: 10.7314/apjcp.2015.16.15.6535.
This study was designed to assess, whether a new chemotherapeutic microtubule inhibitor, Epothilone B (EpoB, Patupilone), can induce DNA damage in normal ovarian cells (MM14.Ov), and to evaluate if such damage could be repaired. The changes were compared with the effect of paclitaxel (PTX) commonly employed in the clinic. The alkaline comet assay technique and TUNEL assay were used. The kinetics of DNA damage formation and the level of apoptotic cells were determined after treatment with IC50 concentrations of EpoB and PTX. It was observed that PTX generated significantly higher apoptotic and genotoxic changes than EpoB. The peak was observed after 48 h of treatment when the DNA damage had a maximal level. The DNA damage induced by both tested drugs was almost completely repaired. As EpoB in normal cells causes less damage to DNA it might be a promising anticancer drug with potential for the treatment of ovarian tumors.
本研究旨在评估一种新型化疗微管抑制剂埃坡霉素B(EpoB,帕土匹隆)是否能诱导正常卵巢细胞(MM14.Ov)发生DNA损伤,并评估这种损伤是否能够修复。将这些变化与临床常用的紫杉醇(PTX)的作用效果进行比较。采用碱性彗星试验技术和TUNEL试验。在用EpoB和PTX的IC50浓度处理后,测定DNA损伤形成的动力学和凋亡细胞水平。观察到PTX产生的凋亡和遗传毒性变化明显高于EpoB。在处理48小时后观察到峰值,此时DNA损伤达到最大水平。两种受试药物诱导的DNA损伤几乎完全得到修复。由于EpoB对正常细胞中的DNA造成的损伤较小,它可能是一种有前景的抗癌药物,具有治疗卵巢肿瘤的潜力。