Laboratory of Radiobiology and Tumor Biology, Chiricuta Cancer Institute, Cluj-Napoca, Romania.
Cell Biochem Funct. 2011 Jul;29(5):351-5. doi: 10.1002/cbf.1754. Epub 2011 Apr 13.
Despite the notable efficacy of oxaliplatin in the treatment of colorectal cancers, the metastatic tumours ultimately become resistant to the drug. This study investigated whether the oxaliplatin-resistant cells display different behaviour to this drug versus the sensitive cells and if this difference may be further exploited into the clinical treatments improvement. In order to establish a stable cell line resistant to oxaliplatin, a human colorectal cancer cell line (Colo320) was exposed to increasing doses of the drug up to the clinically relevant plasma concentration. Four cell groups with different levels of chemoresistance were subjected to additional doses of oxaliplatin, and their cytotoxicity, apoptosis and DNA damage production were assessed. Cells selected for resistance to oxaliplatin reacted differently to the application of additional doses of the drug, displaying lower toxicity and cellular death and fewer DNA cross-links formation, in accordance with the extent of the oxaliplatin pretreatments. As the cross-links formation by oxaliplatin being the main cause for cytotoxicity of this drug and a correlation between cytotoxicity and clinical outcome being shown repeatedly, we consider that the evaluation of oxaliplatin-induced cytotoxicity, apoptosis and DNA damage could be a valuable tool to assess the tumour cells sensitivity and thus to predict the response to chemotherapy.
尽管奥沙利铂在治疗结直肠癌方面具有显著疗效，但转移性肿瘤最终会对该药物产生耐药性。本研究旨在探讨奥沙利铂耐药细胞对该药物的反应是否与敏感细胞不同，以及这种差异是否可以进一步应用于临床治疗的改善。
为了建立稳定的奥沙利铂耐药细胞系，将人结直肠癌细胞系（Colo320）暴露于递增剂量的药物，直至达到临床相关的血浆浓度。将四个具有不同化疗耐药程度的细胞组接受额外剂量的奥沙利铂，并评估其细胞毒性、细胞凋亡和 DNA 损伤的产生。
对奥沙利铂耐药的细胞对额外剂量药物的反应不同，表现出较低的毒性和细胞死亡，以及较少的 DNA 交联形成，与奥沙利铂预处理的程度一致。由于奥沙利铂的交联形成是该药物细胞毒性的主要原因，并且细胞毒性与临床结果之间的相关性已被反复证明，我们认为评估奥沙利铂诱导的细胞毒性、细胞凋亡和 DNA 损伤可能是评估肿瘤细胞敏感性的有用工具，从而可以预测对化疗的反应。
