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Enhanced cytotoxicity of bleomycin and cisplatin after electroporation in murine colorectal carcinoma cells

机译:电击后博来霉素和顺铂对小鼠结肠直肠癌细胞的细胞毒性增强

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Background. Electrochemotherapy is a local treatment combining application of electric pulses and chemotherapy. Two chemotherapeutic drugs, bleomycin and cisplatin, have proved to be effective in electrochemotherapy. The effectiveness of electrochemotherapy was demonstrated in the treatment of various cutaneous and subcutaneous tumours in cancer patients. Only a few preclinical studies were performed in colorectal carcinoma, mostly using bleomycin. Our aim was to evaluate the sensitivity of the murine colorectal carcinoma cell line CMT-93 to electrochemotherapy with bleomycin and cisplatin for potential use in preclinical and clinical studies.Methods. CMT-93 cells were exposed to either the chemotherapeutic drug alone or electrochemotherapy. A clonogenic assay was used to determine cell survival after treatment. Apoptosis was measured by caspase-3/7 activity, necrosis by changes in cell morphology and cell viability by the MTS assay 16 hours after electrochemotherapy.Results. Cells treated with electrochemotherapy were 500-fold more sensitive to bleomycin and 2.8-fold more sensitive to cisplatin compared to cells treated with the drugs alone. At the highest concentrations, a significant reduction in cell viability, increase in caspase-3/7 activity and necrotic cells were observed after electrochemotherapy.Conclusions. Exposure of cells to electric pulses enhanced cytotoxicity of both bleomycin and cisplatin. Reduced cell viability was due to apoptotic and necrotic cell death. Furthermore, electrochemotherapy with bleomycin was more cytotoxic than electrochemotherapy with cisplatin in this colorectal carcinoma cell line.
机译:背景。电化学疗法是结合电脉冲和化学疗法的局部治疗。事实证明,博莱霉素和顺铂这两种化学疗法在电化学疗法中是有效的。在癌症患者的各种皮肤和皮下肿瘤的治疗中证明了电化学疗法的有效性。在结直肠癌中仅进行了少数临床前研究,大部分使用博来霉素。我们的目的是评估鼠结直肠癌细胞系CMT-93对博来霉素和顺铂电化学疗法的敏感性,以用于临床前和临床研究。将CMT-93细胞单独接受化学治疗或电化学疗法。使用克隆形成测定法来确定处理后的细胞存活。化疗16小时后,通过caspase-3 / 7活性测量细胞凋亡,通过细胞形态变化和细胞活力通过MTS测定测量坏死。与单独用药物处理的细胞相比,用电化学疗法处理的细胞对博来霉素的敏感性高500倍,对顺铂的敏感性高2.8倍。在最高浓度下,电化学疗法后观察到细胞活力显着降低,caspase-3 / 7活性增加和坏死细胞。将细胞暴露于电脉冲会增强博来霉素和顺铂的细胞毒性。细胞活力降低是由于凋亡和坏死细胞死亡。此外,在该结肠直肠癌细胞系中,博来霉素电化学疗法比顺铂电化学疗法更具细胞毒性。

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