骨肉瘤细胞中参与顺铂获得性耐药相关基因鉴定的表达分析
Expression Analysis for the Identification of Genes Involved in Acquired Resistance to Cisplatin in Osteosarcoma Cells.
作者信息
Takazawa Koutarou, Tsuchiya Hiroyuki, Yoshimichi Ueda, Kanazawa Yoshimitsu, Ii Sadao, Tomita Katsuro
机构信息
Department of Orthopaedic Surgery, Graduate School of Medical Science, Kanazawa University, 13-1 Takara-machi, Kanazawa.
Department of Pathology, Kanazawa Medical University, 1-1 Uchidana-machi, Kahoku-gun, Ishikawa, Japan.
出版信息
Cancer Genomics Proteomics. 2006 Nov-Dec;3(6):373-381. Epub 2006 Nov 1.
BACKGROUND
Clinical observations indicate that tumour cells can acquire tolerance when an anticancer drug is administered repeatedly. In the present study, the gene expression in cisplatin-resistant cells was analysed to identify early changes in gene expression in the course of cisplatin exposure.
MATERIALS AND METHODS
After establishing a cisplatin-resistant human osteosarcoma subline (OST/R) and two additional sublines by more brief repeated exposure, cDNA expression microarrays were used to study genes linked with prolonged exposure to cisplatin of human cancer cells.
RESULTS
OST/R cells showed increased expression of 17 genes and reduced expression of 14. Genes associated with DNA repair, apoptosis, cell cycle progression, and proliferation were associated with the acquired resistance. Genes showing early changes were also identified.
CONCLUSION
Identification of genes showing altered expression in the early stages of development of resistance to cisplatin may help to improve the therapeutic effectiveness of this drug.
背景
临床观察表明，反复给予抗癌药物时肿瘤细胞可获得耐受性。在本研究中，分析了顺铂耐药细胞中的基因表达，以确定顺铂暴露过程中基因表达的早期变化。
材料与方法
通过更短暂的反复暴露建立顺铂耐药人骨肉瘤亚系（OST/R）和另外两个亚系后，利用cDNA表达微阵列研究与人类癌细胞长期暴露于顺铂相关的基因。
结果
OST/R细胞中17个基因表达增加，14个基因表达减少。与DNA修复、凋亡、细胞周期进程和增殖相关的基因与获得性耐药有关。还鉴定出了显示早期变化的基因。
结论
鉴定在顺铂耐药发展早期表达改变的基因可能有助于提高该药物的治疗效果。
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