Differential sensitivity to paclitaxel-induced apoptosis and growth suppression in paclitaxel-resistant cell lines established from HEC-1 human endometrial adenocarcinoma cells
Differential sensitivity to paclitaxel-induced apoptosis and growth suppression in paclitaxel-resistant cell lines established from HEC-1 human endometrial adenocarcinoma cells
复制标题
DOI：
10.3892/ijo.2012.1600
复制
发表时间：
2012-11-01
影响因子：
5.2
通讯作者：
Tanaka, Junko
中科院分区：
文献类型：
--
作者：
Tanaka, Tetsuji;Toujima, Saori;Tanaka, Junko
为了研究肿瘤细胞对紫杉醇（PTX）的获得性耐药，我们从HEC-1人子宫内膜腺癌细胞中建立了5株单克隆PTX耐药细胞系。已建立的PTX抗性亚克隆对PTX诱导的DNA片段化表现出明显的抗性，但对PTX诱导的生长抑制没有抗性。五个紫杉醇耐药亚克隆均未对其他抗癌药物（例如顺铂、依托泊苷、5-氟尿嘧啶、吡柔比星-HC 1、4-羟基-环磷酰胺或丝裂霉素C）表现出明显的耐药性。半定量流式细胞仪分析显示，没有明显的差异表达的17个分子，以前报道，以调节细胞凋亡或耐药性，之间的5个PTX耐药亚克隆和亲本细胞。核型分析显示，在5个PTX耐药亚克隆中，4号和18号染色体发生了共同的变化，但在HEC-1亲本细胞中没有发生。这些结果表明，PTX诱导的生长抑制是由不同的机制参与PTX诱导的细胞凋亡。得出的结论是，这些建立的PTX耐药亚克隆可以在PTX化疗后复发性癌症的预防或治疗相关的研究中是有用的模型。
To investigate acquired paclitaxel (PTX) resistance in cancer cells, we established five monoclonal PTX-resistant cell lines from HEC-1 human endometrial adenocarcinoma cells by means of long-term PTX-exposed cultures and limiting dilution cultures. The established PTX-resistant subclones showed apparent resistance to PTX-induced DNA fragmentation but not to PTX-induced growth suppression. None of the five PTX-resistant subclones showed apparent resistance to other anticancer drugs such as cisplatin, etoposide, 5-fluorouracil, pirarubicin-HC1, 4-hydroxy-cyclophosphamide or mitomycin C. Semiquantitative flow cytometric analysis revealed no apparent differential expression of 17 molecules that were previously reported to regulate apoptosis or drug resistance, between the five PTX-resistant subclones and the parent cells. Karyotyping analysis revealed common changes in chromosomes 4 and 18 in the five PTX-resistant subclones but not in the HEC-1 parent cells. These results indicate that PTX-induced growth suppression is regulated by different mechanisms from those involved in PTX-induced apoptosis. It was concluded that these established PTX-resistant subclones can be useful models in studies related to the prevention or treatment of recurrent cancers after PTX chemotherapy.