Gene expressions associated with chemosensitivity in human hepatoma cells.
Gene expressions associated with chemosensitivity in human hepatoma cells.
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发表时间：
2007-03
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通讯作者：
Y. Hoshida;M. Moriyama;M. Otsuka;N. Kato;Hiroyoshi Taniguchi;Y. Shiratori;N. Seki;M. Omata
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作者：
Y. Hoshida;M. Moriyama;M. Otsuka;N. Kato;Hiroyoshi Taniguchi;Y. Shiratori;N. Seki;M. Omata
只有有限的肝癌患者从化疗中获益，但没有明确的解释。我们的目的是利用转录谱来鉴定与化疗敏感性相关的基因。方法：应用包含2300个基因的cDNA微阵列技术，在8个肝癌细胞（HLE、HLF、Huh 7、Hep 3B、PLC/PRF/5、SK-Hep 1、Huh 6和HepG 2）中获得转录谱。采用MTT法测定细胞对8种抗癌药物（尼莫司汀、丝裂霉素C、顺铂、卡铂、阿霉素、表阿霉素、米托蒽醌和5-氟尿嘧啶）的50%生长抑制浓度（GI 50）。选择与化疗敏感性具有药物特异性关联的基因。结果拓扑异构酶II β的表达上调与阿霉素的靶点化疗耐药有关。铂特异性耐药与超氧化物歧化酶2表达相关。抗原肽转运蛋白1表达与尼莫司汀和米托蒽醌特异性敏感性相关。这些结果通过半定量RT-PCR验证。在非肝癌中报道的药物灭活剂如多药转运蛋白和药物代谢物在肝癌细胞中的化疗敏感性差异较小。结论对这些基因表达的研究有助于筛选抗肿瘤药物，并可能考虑新的治疗靶点以改变药物的作用。
BACKGROUND/AIMS Only limited patients with hepatoma benefit from chemotherapy without a clear explanation. We aimed to identify genes associated with chemosensitivity using transcriptional profiles. METHODOLOGY In 8 hepatoma cells (HLE, HLF, Huh7, Hep3B, PLC/PRF/5, SK-Hep1, Huh6, and HepG2) transcriptional profiles were obtained using cDNA microarray including 2300 genes. Chemosensitivities to 8 anticancer drugs (nimustine, mitomycin C, cisplatin, carboplatin, doxorubicin, epirubicin, mitoxantrone, and 5-fluorouracil) were measured by obtaining 50% growth inhibitory concentrations (GI50) using MTT assay. Genes having drug-specific association with chemosensitivity were selected. RESULTS Up-regulation of topoisomerase II beta was associated with chemo-resistance, the target of doxorubicin. Platinum-specific resistance was associated with superoxide dismutase 2 expression. Antigen peptide transporter 1 expression correlated with nimustine and mitoxantrone-specific susceptibility. These results were verified by semi-quantitative RT-PCR. Drug inactivators reported in non-liver cancers such as multidrug transporters and drug metabolizers showed less diversity of chemosensitivity in hepatoma cells. CONCLUSIONS To evaluate these gene expressions may be useful to select anticancer drugs, and possibly to consider new therapeutic target to modify drug action.