Gajski Goran, Čimbora-Zovko Tamara, Rak Sanjica, Osmak Maja, Garaj-Vrhovac Vera
Mutagenesis Unit, Institute for Medical Research and Occupational Health, Ksaverska cesta 2, 10000, Zagreb, Croatia.
Laboratory for Genotoxic Agents, Division of Molecular Biology, Ruđer Bošković Institute, Bijenička cesta 54, 10000, Zagreb, Croatia.
Cytotechnology. 2016 Aug;68(4):1197-205. doi: 10.1007/s10616-015-9879-4. Epub 2015 Apr 28.
Cisplatin (cDDP) is one of the most widely used anticancer-drugs in both therapy and research. However, cDDP-resistance is the greatest obstacle for the successful treatment of cancer patients. In the present study, the possible joint anticancer effect of bee venom (BV), as a natural toxin, and cDDP towards human glioblastoma A1235 cells was evaluated. Treatment with BV alone in concentrations of 2.5-30 μg/ml displayed dose-dependent cytotoxicity towards A1235 cells, as evaluated with different cytotoxicity assays (MTT, Cristal violet and Trypan blue exclusion assay), with an IC50 value of 22.57 μg/ml based on the MTT results. Furthermore, BV treatment induced necrosis, which was confirmed by typical morphological features and fast staining with ethidium-bromide dye. Pre-treatment with BV induced cell sensitization to cDDP, indicating that BV could improve the killing effect of selected cells when combined with cDDP. The isobologram method used to determine the extent of synergism in combining two agents to examine their possible therapeutic effect showed that combined treatment induced an additive and/or synergistic effect towards selected cells depending on the concentration of both. Hence, a greater anticancer effect could be triggered if BV was used in the course of chemotherapy. The obtained results indicate that joint treatment with BV could be useful from the point of minimizing the cDDP concentration during chemotherapy, thus reducing and/or postponing the development of drug resistance. Our data, in accordance with previously reported results, suggests that BV could be used in the development of a new strategy for cancer treatment.
顺铂(cDDP)是治疗和研究中使用最广泛的抗癌药物之一。然而,顺铂耐药性是成功治疗癌症患者的最大障碍。在本研究中,评估了作为天然毒素的蜂毒(BV)与顺铂对人胶质母细胞瘤A1235细胞可能的联合抗癌作用。用不同的细胞毒性测定法(MTT、结晶紫和台盼蓝排斥试验)评估,单独使用浓度为2.5 - 30μg/ml的BV对A1235细胞显示出剂量依赖性细胞毒性,基于MTT结果,IC50值为22.57μg/ml。此外,BV处理诱导细胞坏死,这通过典型的形态学特征和用溴化乙锭染料快速染色得到证实。BV预处理诱导细胞对顺铂敏感,表明BV与顺铂联合使用时可提高对所选细胞的杀伤效果。用于确定两种药物联合时协同作用程度以检查其可能治疗效果的等效线图法表明,联合处理对所选细胞诱导了相加和/或协同作用,这取决于两者的浓度。因此,如果在化疗过程中使用BV,可能会引发更大的抗癌效果。获得的结果表明,联合使用BV可能有助于在化疗期间将顺铂浓度降至最低,从而减少和/或推迟耐药性的发展。我们的数据与先前报道的结果一致,表明BV可用于开发新的癌症治疗策略。